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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
in the eye of experimental cerebral malaria.cerebral malaria is the most severe complication of plasmodium falciparum infection, accounting for 1 million deaths per year. we characterized the murine disease using in vivo magnetic resonance imaging (mri) at 4.7 t, proving that ischemic edema is responsible for fatality. the aim of the present study was to identify early markers of experimental cerebral malaria using very high field conventional mri (11.75 t). cba/j mice infected with plasmodium berghei anka were observed at an early stage ...201121741941
investigations on the role of a lysozyme from the malaria vector anopheles dirus during malaria parasite development.a cdna encoding a lysozyme was obtained by rapid amplification of cdna ends-polymerase chain reaction (race-pcr) from females of the malaria vector anopheles dirus a (diptera: culicidae). the 623bp lysozyme (adlys c-1) cdna encodes the 120 amino acid mature protein with a predicted molecular mass of 13.4kda and theoretical pi of 8.45. six cysteine residues and a potential calcium binding motif that are present in adlys c-1 are highly conserved relative to those of c-type lysozymes found in other ...201121741400
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
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
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
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
antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in plasmodium berghei-infected mice.artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (acts). however, acts are expensive and some of the non-artemisinin components are not well-tolerated by patients. there are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. mature leaves of carica papaya is widely used to treat malaria in several african countries. an act involving a medicin ...201121715732
cd8+ t effector memory cells protect against liver-stage malaria.identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. we investigated protection against liver-stage malaria conferred by vaccination with adenoviral (ad) and modified vaccinia ankara (mva) vectors expressing pre-erythrocytic malaria ags. by classifying cd8(+) t cells into effector, effector memory (t(em)), and central memory subsets using cd62l and cd127 markers, we fou ...201121715686
lessons from sickle cell disease in the treatment and control of malaria. 201121714653
caspase-1 activation of interleukin-1{beta} (il-1{beta}) and il-18 is dispensable for induction of experimental cerebral malaria.malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be "clinically and diagnostically silent." merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. how the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. likewise, how the initial liver stages may shape responses to blood-stage pa ...201121708993
toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent il-1╬▓ secretion enhances parasite replication.abstract: alternatively activated macrophages (aam) are a key feature th2 immunity and have been associated with a variety of roles during helminth infection. the role this cell subset plays in protzoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rtgprx) derived from toxoplasma gondii on murine macrophage phenotype in vitro. rtgprx has been previously associated with the maintainence of parasite oxidative balance. here our experiments show that rtgpr ...201121707997
improvement of the observational method for plasmodium berghei oocysts in the midgut of mosquitoes.there is a need for improving the method for counting oocysts of plasmodium berghei in the midgut of anopheles mosquitoes. the two methods currently used, the formalin fixation method and the mercurochrome staining method, have contradicting advantages and disadvantages. in the formalin fixation method, the specimen can be preserved but unstained oocysts were often indistinct from the insect tissue. while in the mercurochrome staining method, stained oocysts can be clearly distinguished from ins ...201121707972
4-aminoquinoline analogues and its platinum (ii) complexes as antimalarial agents.the high incidence of malaria and drug-resistant strains of plasmodium have turned this disease into a problem of major health importance. one of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. this class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of +¦-haematin (malaria pigment), which is lethal to the parasite. more specifically, 4-aminoquinoline derivates represent ...201121704476
resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.the greatest impediment to effective malaria control is drug resistance in plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy.201121698180
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
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
apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in toxoplasma gondii.apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. apicomplexan parasites contain a relict chloroplast, the apicoplast. the apicoplast is indispensable and an attractive drug target. the apicoplast is home to a 1-deoxy-d-xylulose-5-phosphate (doxp) pathway for the synthesis of isoprenoid precursors. this pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathwa ...201121690250
characterization of a new phosphatase from plasmodium.plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. two p. falciparum genes code for putative phosphoglycerate mutases (pgmases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. pgmases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. we have determined the crystal structures o ...201121689687
glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen plasmodium falciparum in culture and against plasmodium berghei in infected mice. with respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initia ...201121682307
type i interferons suppress cd4(+) t-cell-dependent parasite control during blood-stage plasmodium infection.during blood-stage plasmodium infection, large-scale invasion of rbcs often occurs before the generation of cellular immune responses. in plasmodium berghei anka (pba)-infected c57bl/6 mice, cd4(+) t cells controlled parasite numbers poorly, instead providing early help to pathogenic cd8(+) t cells. expression analysis revealed that the transcriptional signature of cd4(+) t cells from pba-infected mice was dominated by type i ifn (ifn-i) and ifn-╬│-signalling pathway-related genes. a role for if ...201121674481
the puf-family rna-binding protein puf2 controls sporozoite conversion to liver stages in the malaria parasite.malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus plasmodium. during host switch the malaria parasite employs specialized latent stages that colonize the new host environment. previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. sexual parasite development is controlled by a ...201121673790
superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites.while subunit vaccines have shown partial efficacy in clinical trials, radiation-attenuated sporozoites (ras) remain the "gold standard" for sterilizing protection against plasmodium infection in human vaccinees. the variability in immunogenicity and replication introduced by the extensive, random dna damage necessary to generate ras could be overcome by genetically attenuated parasites (gap) designed via gene deletion to arrest at defined points during liver-stage development. here, we demonstr ...201121669394
genetic and transcriptional analysis of phosphoinositide-specific phospholipase c in plasmodium.phosphoinositide-specific phospholipase c (pi-plc) is a major regulator of calcium-dependent signal transduction, which has been shown to be important in various processes of the malaria parasite plasmodium. pi-plc is generally implicated in calcium liberation from intracellular stores through the action of its product, inositol-(1,4,5)-trisphosphate, and is itself dependent on calcium for its activation. here we describe the plc genes from plasmodium species. the encoded proteins contain all do ...201121651909
alternative splicing of the anopheles gambiae dscam gene in diverse plasmodium falciparum infections.in insects, including anopheles mosquitoes, dscam (down syndrome cell adhesion molecule) appears to be involved in phagocytosis of pathogens, and shows pathogen-specific splice-form expression between divergent pathogen (or parasite) types (e.g. between bacteria and plasmodium or between plasmodium berghei and plasmodium falciparum). here, data are presented from the first study of dscam expression in response to genetic diversity within a parasite species.201121651790
exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during plasmodium berghei anka infection in mice.abstract: background: cerebral malaria (cm) is a lethal complication of plasmodium falciparum infections. in the plasmodium berghei anka (pba) murine model, cm is associated with marked brain inflammation, increased expression of endothelial cell adhesion molecules and leukocyte and platelet accumulation in brain vessels, causing vascular occlusion and decreased blood flow, damaging the endothelium and leading to blood-brain barrier breakdown, leakage and hemorrhages. exogenous nitric oxide (no) ...201121649904
pharmacokinetics, pharmacodynamics and allometric scaling of chloroquine in a murine malaria model.chloroquine (cq) is an important antimalarial drug for the treatment of special patient groups and as a comparator for pre-clinical testing of new drugs. pharmacokinetic data for cq in animal models are limited, hence we conducted a three-part investigation, comprising: (i) pharmacodynamic studies of cq and cq plus dihydroartemisinin (dha) in plasmodium berghei infected mice; (ii) pharmacokinetic studies of cq in healthy and malaria-infected mice; and (iii) interspecies allometric scaling for cq ...201121646487
imidazolopiperazines (i): optimization for new antimalarial agents.starting from a hit series from a gnf compound library collection and based on a cell-based proliferation assay of plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. sar for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. the lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. ...201121644570
antimalarial pyrido[1,2-a]benzimidazoles.a novel class of antimalarial pyrido[1,2-a]benzimidazoles were synthesized and evaluated for antiplasmodial activity and cytotoxicity following hits identified from screening commercially available compound collections. the most active of these, tdr86919 (4c), showed improved in vitro activity v the drug-resistant k1 strain of plasmodium falciparum relative to chloroquine (ic50 = 0.047 µm v 0.17 µm); potency was retained against a range of drug-sensitive and drug-resistant strains, with negligib ...201121644541
synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives.a series of 2-guanidino-4-oxoimidazoline (deoxo-iz) derivatives was prepared and showed potent antimalarial activities in rodent and rhesus models. compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in rhesus monkeys infected with sporozoites of plasmodium cynomolgi. the meta ...201121627120
transition of plasmodium sporozoites into liver stage-like forms is regulated by the rna binding protein pumilio.many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve rna binding proteins as regulators of translation of key mrnas. in malaria parasites (plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. ...201121625527
plasmodium berghei proteome changes in response to ssj-183 treatment.the benzo[a]phenoxazine derivative, ssj-183 has shown excellent anti-malarial efficacy and safety. however, its mechanism of action is unclear. we investigated the effect of ssj-183 on the rodent malarial parasite, plasmodium berghei. we analyzed changes in protein expression in the erythrocytic cycle of p. berghei with or without 18h of ssj-183 treatment by two-dimensional gel electrophoresis. we confirmed results with matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flig ...201121622001
synthesis and biological screening of some pyridine derivatives as anti-malarial agents.two series of pyridine derivatives were synthesised and evaluated for their in vivo anti-malarial activity against plasmodium berghei. the anti-malarial activity was determined in vivo by applying 4-day standard suppressive test using chloroquine (cq)-sensitive p. berghei anka strain-infected mice. compounds 2a, 2g and 2h showed inhibition of the parasite multiplication by 90, 91 and 80%, respectively, at a dose level of 50 µmol/kg. moreover, the most active compounds (2a, 2g and 2h) were tested ...201121612373
induction of pro-inflammatory mediators in plasmodium berghei infected balb/c mice breaks blood-brain-barrier and leads to cerebral malaria in an il-12 dependent manner.a severe complication of plasmodium infection is cerebral malaria, a condition mainly attributed to overwhelming inflammatory immune reactions of the host. murine models differing in susceptibility to experimental cerebral malaria (ecm) allow detailed studies of the host response. we show that ecm- resistant balb/c mice were driven into interferon gamma- and il-12-dependent ecm and subsequent death if they received cpg-oligonucleotides after plasmodium berghei anka (pba) infection. cpg applicati ...201121609776
plasmodium berghei induces apoptotic changes in splenic and peripheral blood cells.intracellular parasites manipulate host cell apoptosis in different ways either to increase their life span within infected cells or to spread infection. the present data provided information on the cellular changes taking place in spleen and peripheral blood during plasmodium berghei-infection and indicated apoptosis mediated host immune response during infection. our results suggested a significant change in cellular composition and absolute number of white blood cells in spleen and peripheral ...201121602777
effects of plasmodium berghei on thymus: high levels of apoptosis and premature egress of cd4(+)cd8(+) thymocytes in experimentally infected mice.we have previously showed alterations in the thymus during experimental infection with plasmodium berghei, the causative agent of malaria. such alterations comprised histological changes with loss of delimitation between cortical and medullar regions, a profound atrophy with depletion of cd4(+)cd8(+) double-positive (dp) thymocytes, and severe changes in the expression of cell migration-related molecules, belonging to the extracellular matrix and chemokine protein families. taken together, these ...201121601941
anti-malarial effect of gum arabic.abstract: background: gum arabic (ga), a nonabsorbable nutrient from the exudate of acacia senegal, exerts a powerful immunomodulatory effect on dendritic cells, antigen-presenting cells involved in the initiation of both innate and adaptive immunity. on the other hand ga degradation delivers short chain fatty acids, which in turn have been shown to foster the expression of foetal haemoglobin in erythrocytes. increased levels of erythrocyte foetal haemoglobin are known to impede the intraerythro ...201121599958
a new class of phenazines with activity against a chloroquine resistant plasmodium falciparum strain and antimicrobial activity.a series of new phenazines was synthesized by oxygenation of 1- and 2-naphthol with transition metal peroxo complexes and in situ reaction with 1,2-diamines. the phenazines 7-10 and 17 and 18 were derived from the corresponding 1,2-naphthoquinones, compounds 11-14, 19-25, 27-29, 31, and 32 from the corresponding "dimeric" 1,2-naphthoquinones and phenazines 33, 37, and 41 from related 1,2-diones or 1,4 diones. the title compounds were evaluated for in vitro antimalarial activity against plasmodiu ...201121591758
fosmidomycin uptake into plasmodium and babesia-infected erythrocytes is facilitated by parasite-induced new permeability pathways.highly charged compounds typically suffer from low membrane permeability and thus are generally regarded as sub-optimal drug candidates. nonetheless, the highly charged drug fosmidomycin and its more active methyl-derivative fr900098 have proven parasiticidal activity against erythrocytic stages of the malaria parasite plasmodium falciparum. both compounds target the isoprenoid biosynthesis pathway present in bacteria and plastid-bearing organisms, like apicomplexan parasites. surprisingly, the ...201121573242
a new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in anopheles mosquitoes.plasmodium requires an obligatory life stage in its mosquito host. the parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.201121573077
natural microbe-mediated refractoriness to plasmodium infection in anopheles gambiae.malaria parasite transmission depends on the successful transition of plasmodium through discrete developmental stages in the lumen of the mosquito midgut. like the human intestinal tract, the mosquito midgut contains a diverse microbial flora, which may compromise the ability of plasmodium to establish infection. we have identified an enterobacter bacterium isolated from wild mosquito populations in zambia that renders the mosquito resistant to infection with the human malaria parasite plasmodi ...201121566196
functional genetics in apicomplexa: potentials and limits.the apicomplexans are obligate intracellular protozoan parasites and the causative agents of severe diseases in humans and animals. although complete genome sequences are available since many years and for several parasites, they are replete with putative genes of unassigned function. forward and reverse genetic approaches are limited only to a few apicomplexans that can either be propagated in vitro or in a convenient animal model. this review will compare and contrast the most recent strategie ...201121557944
s1p is associated with protection in human and experimental cerebral malaria.cerebral malaria (cm) is associated with excessive inflammatory responses and endothelial activation. sphingosine 1-phosphate (s1p) is a signaling sphingolipid implicated in regulating vascular integrity, inflammation and t cell migration. we hypothesized that altered s1p signaling during malaria contributes to endothelial activation and inflammation, and show that plasma s1p levels were decreased in ugandan children with cm compared to children with uncomplicated malaria. using the plasmodium b ...201121556483
selection of drug resistant mutants from random library of plasmodium falciparum dihydrofolate reductase in plasmodium berghei model.abstract:201121554743
structure-function analysis of the anopheles gambiae lrim1/apl1c complex and its interaction with complement c3-like protein tep1.malaria threatens half the world's population and exacts a devastating human toll. the principal malaria vector in africa, the mosquito anopheles gambiae, encodes 24 members of a recently identified family of leucine-rich repeat proteins named lrims. two members of this family, lrim1 and apl1c, are crucial components of the mosquito complement-like pathway that is important for immune defense against plasmodium parasites. lrim1 and apl1c circulate in the hemolymph exclusively as a disulfide-bond ...201121533217
sickle hemoglobin confers tolerance to plasmodium infection.sickle human hemoglobin (hb) confers a survival advantage to individuals living in endemic areas of malaria, the disease caused by plasmodium infection. as demonstrated hereby, mice expressing sickle hb do not succumb to experimental cerebral malaria (ecm). this protective effect is exerted irrespectively of parasite load, revealing that sickle hb confers host tolerance to plasmodium infection. sickle hb induces the expression of heme oxygenase-1 (ho-1) in hematopoietic cells, via a mechanism in ...201121529713
multiple roles for plasmodium berghei phosphoinositide-specific phospholipase c in regulating gametocyte activation and differentiation.critical events in the life cycle of malaria parasites are controlled by calcium-dependent signalling cascades, yet the molecular mechanisms of calcium release remain poorly understood. the synchronized development of plasmodium berghei gametocytes relies on rapid calcium release from internal stores within 10 s of gametocytes being exposed to mosquito-derived xanthurenic acid (xa). here we addressed the function of phosphoinositide-specific phospholipase c (pi-plc) for regulating gametocyte act ...201121518218
lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice.malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. we previously reported identification of a new class of triazolopyrimidine-based plasmodium falciparum dihydroorotate dehydrogenase (pfdhodh) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. active compounds from the ...201121517059
antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (n-251) against p. falciparum and plasmodium berghei parasites. the n-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (ec(50) 2.3×10(-8) m; ed(50) 1 ...201121501696
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
suppression of plasmodium berghei parasitemia by licl in an animal infection model.malaria, caused by the plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. the search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant plasmodium falciparum strains. protein kinases such as mitogen-activated protein kinase (mapk), mapk kinase, cyclin-dependent kinase (cdk) and glycogen synthase kinase- 3(gsk-3) of parasitic protozoa are potential drug targets. gsk-3 is an enzyme that ...201021399604
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
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
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
[cryopreservation of plasmodia with malaria models and establishment of a cryobank.]objective: cryopreservation is simply a method of keeping living cells frozen with the chance of regaining cellular viability, functions and antigenic structures whenever required, after heating. methods: in the present study, dimethyl sulphoxide (dmso) was mixed with the red blood cells having 20% of parasitemia obtained from the mice infected with plasmodium yoelii and plasmodium berghei at a final concentration of 15%. for cryopreservation: both test tubes containing each plasmodium species w ...201021391181
characterization of plasmodium berghei glutathione synthetase.plasmodium berghei contained 0.454±0.031 u/mg of glutathione synthetyase (gs). gs was purified using solid ammonium sulfate and sephadex g-200 from p. berghei infected mouse erythrocytes. sds-page showed purified gs as a single band protein of 70 kda and its km for ?-glutamylcysteine, glycine and atp being 0.33 mm, 8.3 mm and 0.43 mm respectively with noncompetitive inhibition by gsh. the malaria parasite enzyme was optimally active at 37°c and ph 8.0-8.5. heavy metals significantly inhibited pa ...201121377539
activation of a pak-mek signalling pathway in malaria parasite-infected erythrocytes.merozoites of malaria parasites invade red blood cells (rbcs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for malaria pathogenesis. here, we report that a protein kinase-mediated signalling pathway involving host rbc pak1 and mek1, which do not have orthologues in the plasmodium kinome, is selectively stimulated in plasmodium falciparum-infected (versus uninfected) rbcs, as determined by the use of phospho-specific ...201121371233
in vitro and in vivo antiplasmodial activities of risedronate and its interference with protein prenylation in plasmodium falciparum.the increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of plasmodium falciparum (50% inhibitory concentration [ic50] of 20.3±1.0 µm). we also suggest a mechanism of action for risedronate against the intraerythrocytic sta ...201121357292
cutting edge: attrition of plasmodium-specific memory cd8 t cells results in decreased protection that is rescued by booster immunization.sterile protection against infection with plasmodium sporozoites requires high numbers of memory cd8 t cells. however, infections with unrelated pathogens, as may occur in areas endemic to malaria, can dramatically decrease pre-existing memory cd8 t cells. it remains unknown whether unrelated infections will compromise numbers of plasmodium-specific memory cd8 t cells and thus limit the duration of antimalarial immunity generated by subunit vaccination. we show that p. berghei circumsporozoite-s ...201121357257
aryl piperazine and pyrrolidine as antimalarial agents. synthesis and investigation of structure-activity relationships.piperazine and pyrrolidine derivatives were synthesised and evaluated for their capacity to inhibit the growth of plasmodium falciparum chloroquine-resistant (fcr-3) strain in culture. the combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses =10 µm. the most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin- ...201121354139
high parasite burdens cause liver damage in mice following plasmodium berghei anka infection independently of cd8(+) t cell-mediated immune pathology.infection of c57bl/6 mice with plasmodium berghei anka induces a fatal neurological disease commonly referred to as experimental cerebral malaria. the onset of neurological symptoms and mortality depend on pathogenic cd8(+) t cells and elevated parasite burdens in the brain. here we provide clear evidence of liver damage in this model, which precedes and is independent of the onset of neurological symptoms. large numbers of parasite-specific cd8(+) t cells accumulated in the liver following p. b ...201121343349
calcium signal regulates temperature-dependent transformation of sporozoites in malaria parasite development.the infection by the malaria parasite of its mammalian host is initiated by the asexual reproduction of the parasite within the host hepatocyte. before the reproduction, the elongated sporozoites undergo a depolarizing morphogenesis to the spherical exo-erythrocytic form (eef). this change can be induced in vitro by shifting the environmental conditions, in the absence of host hepatocytes. using rodent malaria parasites expressing a fret-based calcium sensor, yc3.60, we observed that the intrace ...201121335005
synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents.a series of n'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3h-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit ß-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent plasmodium berghei. selected analogues were screened for their antitubercular activity against sensitive mtb h(37)rv and multidrug-resistant mdr-mtb strains, and cytotoxic activity against a panel of human tumor cell lin ...201121334900
gene profiling analysis reveals the contribution of cd24 and p2y6r to the susceptibility of young rats to plasmodium berghei infection.our previous studies have shown that plasmodium berghei infection induces distinct clinical, parasitological and immunological states in young susceptible rats versus adult resistant rats. this susceptibility was mainly found to be related to inadequate cellular responses. in this study we first identified the altered genes in young susceptible rats. unexpectedly, transcriptome analysis did not reveal any alteration of effector cytokines or their receptors. at day 13 p.i., six transcripts corres ...201121323829
energy metabolism affects susceptibility of anopheles gambiae mosquitoes to plasmodium infection.previous studies showed that anopheles gambiae l3-5 females, which are refractory (r) to plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (s) g3 females. our studies revealed that r females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. furthermore, ...201121320598
ratt: rapid annotation transfer tool.second-generation sequencing technologies have made large-scale sequencing projects commonplace. however, making use of these datasets often requires gene function to be ascribed genome wide. although tool development has kept pace with the changes in sequence production, for tasks such as mapping, de novo assembly or visualization, genome annotation remains a challenge. we have developed a method to rapidly provide accurate annotation for new genomes using previously annotated genomes as a refe ...201121306991
therapeutical targeting of nucleic acid-sensing toll-like receptors prevents experimental cerebral malaria.excessive release of proinflammatory cytokines by innate immune cells is an important component of the pathogenic basis of malaria. proinflammatory cytokines are a direct output of toll-like receptor (tlr) activation during microbial infection. thus, interference with tlr function is likely to render a better clinical outcome by preventing their aberrant activation and the excessive release of inflammatory mediators. herein, we describe the protective effect and mechanism of action of e6446, a s ...201121303985
in vivo and in vitro antimalarial activity of 4-nerolidylcatechol.4-nerolidylcatechol (4-nc) isolated from piper peltatum l. (piperaceae) was evaluated for in vitro antiplasmodial activity against plasmodium falciparum (cultures of both standard cqr (k1) and cqs (3d7) strains and two amazonian field isolates) and for in vivo antimalarial activity using the plasmodium berghei-murine model. 4-nc exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-nc administered orally and subcutaneously at doses of 200, 400 and 600?mg/kg/day suppressed ...201121302338
synthetic ozonide drug candidate oz439 offers new hope for a single-dose cure of uncomplicated malaria.ozonide oz439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. oz439 has successfully completed phase i clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing phase iia trials in malaria patients. herein, we describe the discovery of oz439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. in vitro, oz439 is fast-ac ...201121300861
in vitro and in vivo antiplasmodial activity and cytotoxicity of water extracts of phyllanthus emblica, terminalia chebula, and terminalia bellerica.to evaluate the in vitro and in vivo antiplasmodial activity and the cytotoxicity of phyllanthus emblica linn, terminalia chebula retz, and terminalia bellerica (gaertn) roxb extracts.201021294406
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
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
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
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
new imidazolidinedione derivatives as antimalarial agents.a series of new n-alky- and n-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and rhesus monkey models. new compounds are generally metabolically stable, weakly active in vitro against plasmodium falciparum clones (d6 and w2) and in mice infected with plasmodium berghei sporozoites. representative compounds 8e and 9c showed good causal prophylactic activity in rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by im, delayed pa ...201021282058
evaluation of the use of cocos nucifera as antimalarial remedy in malaysian folk medicine.white flesh extract of cocos nucifera (coconut) was studied to ascertain the ethnopharmacological standing of its antimalarial usage in malaysian folk medicine.201121277969
a chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype a light chain, p. falciparum malaria, and the ebola filovirus.a 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype a light chain metalloprotease. subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the bont/a lc. three-dimensional analyses indicated that half of the originally discovered 1,7-daac structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. thi ...201121265542
screening of antiplasmodial efficacy of ajuga bracteosa wall ex. benth.the rising problem of plasmodium resistance to the classical antimalarial drugs stresses the need to look for newer antiplasmodial components with effective and new mode of action. in the present study, the traditional medicinal plant ajuga bracteosa has been screened for its antiplasmodial efficacy. the extract was found to possess significant in vitro antiplasmodial efficacy with an ic(50) of 10.0 µg/ml. thus, the extract was further evaluated for its in vivo schizontocidal activity and effica ...201121264476
the malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host.plasmodium sporozoites make a remarkable journey from the mosquito midgut to the mammalian liver. the sporozoite's major surface protein, circumsporozoite protein (csp), is a multifunctional protein required for sporozoite development and likely mediates several steps of this journey. in this study, we show that csp has two conformational states, an adhesive conformation in which the c-terminal cell-adhesive domain is exposed and a nonadhesive conformation in which the n terminus masks this doma ...201121262960
anxiety-like behavior and proinflammatory cytokine levels in the brain of c57bl/6 mice infected with plasmodium berghei (strain anka).cerebral malaria (cm) is a severe complication resulting from plasmodium falciparum infection. the underlying mechanisms of cm pathogenesis remain incompletely understood. the imbalance between the release of proinflammatory and anti-inflammatory cytokines has been associated with central nervous system dysfunction found in human and experimental cm. the current study investigated anxiety-like behavior, histopathological changes and release of brain cytokines in c57bl/6 mice infected with plasmo ...201121256928
beta interferon suppresses the development of experimental cerebral malaria.cerebral malaria (cm) is a major complication of plasmodium falciparum infection, particularly in children. the pathogenesis of cerebral malaria involves parasitized red blood cell (rbc)-mediated vascular inflammation, immune stimulation, loss of blood-brain barrier integrity, and obstruction of cerebral capillaries. therefore, blunting vascular inflammation and immune cell recruitment is crucial in limiting the disease course. beta interferon (ifn-β) has been used in the treatment of diseases, ...201121245265
malaria crystalloids: specialized structures for parasite transmission?malaria parasites possess many unique subcellular structures and organelles that are essential for the successful completion of the complex life cycle of plasmodium in the vertebrate host and mosquito vector. among these are the crystalloids: transient structures whose presence is restricted to the mosquito-specific ookinete and young oocyst stages of the parasite. nearly five decades after they were first described, the crystalloids are back in the spotlight, with recent discoveries pointing to ...201121237711
protein kinase c-theta is required for development of experimental cerebral malaria.cerebral malaria is the most severe neurologic complication in children and young adults infected with plasmodium falciparum. t-cell activation is required for development of plasmodium berghei anka (pba)-induced experimental cerebral malaria (cm). to characterize the t-cell activation pathway involved, the role of protein kinase c-theta (pkc-θ) in experimental cm development was examined. pkc-θ-deficient mice are resistant to cm development. in the absence of pkc-θ, no neurologic sign of cm dev ...201021224058
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
triclosan is minimally effective in rodent malaria models. 201121217674
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