Publications

implementation of minimally invasive and objective humane endpoints in the study of murine plasmodium infections.	summary defining appropriate and objective endpoints for animal research can be difficult. previously we evaluated and implemented a body temperature (bt) of <32 °c as an endpoint for experimental cerebral malaria (ecm) and were interested in a similar endpoint for a model of severe malarial anaemia (sma). furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated bt measurement. ecm was induced with plasmodium berghei anka infection in c57bl ...	2014	24993593
systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased calpain and caspase activity and can be reduced by erythropoietin treatment.	the pathogenesis of cerebral malaria (cm) includes compromised microvascular perfusion, increased inflammation, cytoadhesion, and endothelial activation. these events cause blood-brain barrier disruption and neuropathology and associations with the vascular endothelial growth factor (vegf) signaling pathway have been shown. we studied this pathway in mice infected with plasmodium berghei anka causing murine cm with or without the use of erythropoietin (epo) as adjunct therapy. elisa and western ...	2014	24995009
evaluating experimental cerebral malaria using oxidative stress indicator okd48 mice.	cerebral malaria is a fatal complication of malaria. conventional methods for evaluating experimental cerebral malaria have several drawbacks. therefore, we aimed to develop an easy-to-use method for evaluating experimental cerebral malaria using okd48 (keap1-dependent oxidative stress detector, no-48-luciferase) mice to evaluate oxidative stress. okd48 mice infected with plasmodium berghei anka strain (pba) suffered from experimental cerebral malaria and oxidative stress was successfully detect ...	2014	24995619
transcriptome-wide analysis of microrna expression in the malaria mosquito anopheles gambiae.	micrornas (mirnas) are a highly abundant class of small noncoding regulatory rnas that post-transcriptionally regulate gene expression in multicellular organisms. mirnas are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. small-scale studies of mirna expression in the malaria mosquito anopheles gambiae have been reported, however no comprehensive analysis of mirnas has been performed so far.	2014	24997592
dual-stage triterpenoids from an african medicinal plant targeting the malaria parasite.	sixteen triterpenoids (1-16), previously isolated from the aerial parts of the african medicinal plant momordica balsamina or obtained by derivatization, were evaluated for their activity against liver stages of plasmodium berghei, measuring the luminescence intensity in huh-7 cells infected with a firefly luciferase-expressing p. berghei line, pbgfp-luccon. toxicity of compounds (1-16) was assessed on the same cell line through the fluorescence measurement of cell confluency. the highest activi ...	2014	25002232
deletion of c-reactive protein ameliorates experimental cerebral malaria?	c-reactive protein (crp) level correlates with parasitemia and severity of malaria, but whether this reflects causality remains unknown.	2014	25002461
genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.	reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (pps) during plasmodium development are unknown. we report a functional analysis of the plasmodium berghei protein phosphatome, which exhibits high conservation with the p. falciparum phosphatome and comprises 30 predicted pps with differential and distinct expression patt ...	0	25011111
a serine protease homolog negatively regulates tep1 consumption in systemic infections of the malaria vector anopheles gambiae.	clip domain serine protease homologs are widely distributed in insect genomes and play important roles in regulating insect immune responses, yet their exact functions remain poorly understood. here, we show that clipa2, a clip domain serine protease homolog of anopheles gambiae, regulates the consumption of the mosquito complement-like protein tep1 during systemic bacterial infections. we provide evidence that clipa2 localizes to microbial surfaces in a tep1-dependent manner whereby it negative ...	2014	25012124
a novel adjuvant, the mixture of alum and naltrexone, augments vaccine-induced immunity against plasmodium berghei.	we previously showed that the mixture of naltrexone (nlt), a general opioid antagonist, and alum, acts as an effective adjuvant in enhancing vaccine-induced t helper 1 (th1) humoral immune responses against toxoplasma gondii. here, we tested the efficacy of the mixture of nlt and alum in the induction of immunity in response to blood stages of plasmodium berghei (bspb) as a model vaccine. balb/c mice were divided into five vaccination groups. mice in the experimental groups received the bspb vac ...	2014	25020077
bckdh: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of toxoplasma gondii and plasmodium berghei.	while the apicomplexan parasites plasmodium falciparum and toxoplasma gondii are thought to primarily depend on glycolysis for atp synthesis, recent studies have shown that they can fully catabolize glucose in a canonical tca cycle. however, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-coa remains enigmatic. here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase ...	2014	25032958
real-time imaging reveals the dynamics of leukocyte behaviour during experimental cerebral malaria pathogenesis.	during experimental cerebral malaria (ecm) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. the precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. we developed a 2-photon intravital microscopy (2p-ivm)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ecm. ly6c(hi) monocytes, but n ...	2014	25033406
innexin agap001476 is critical for mediating anti-plasmodium responses in anopheles mosquitoes.	the toll and imd pathways are known to be induced upon plasmodium berghei and plasmodium falciparum infection, respectively. it is unclear how plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. this study examined whether innexins, gap ju ...	2014	25035430
antiplasmodial potential of homeopathic drugs chelidonium and nosode against plasmodium berghei infection.	malaria remains a major global health concern in developing regions of the world. homeopathy, a holistic system of medicine, has a lot to offer in protecting against malaria.	2014	25046315
chitinase 3-like 1 is induced by plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case-control study of african children.	severe and fatal malaria are associated with dysregulated host inflammatory responses to infection. chitinase 3-like 1 (chi3l1) is a secreted glycoprotein implicated in regulating immune responses. expression and function of chi3l1 in malaria infection were investigated.	2014	25047113
biochemical and antiparasitic properties of inhibitors of the plasmodium falciparum calcium-dependent protein kinase pfcdpk1.	pfcdpk1 is a plasmodium falciparum calcium-dependent protein kinase, which has been identified as a potential target for novel antimalarial chemotherapeutics. in order to further investigate the role of pfcdpk1, we established a high-throughput in vitro biochemical assay and used it to screen a library of over 35,000 small molecules. five chemical series of inhibitors were initially identified from the screen, from which series 1 and 2 were selected for chemical optimization. indicative of their ...	2014	25070106
iron overload in plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death.	plasmodium infection during gestation may lead to severe clinical manifestations including abortion, stillbirth, intrauterine growth retardation, and low birth weight. mechanisms underlying such poor pregnancy outcomes are still unclear. in the animal model of severe placental malaria (pm), in utero fetal death frequently occurs and mothers often succumb to infection before or immediately after delivery. plasmodium berghei-infected erythrocytes (ies) continuously accumulate in the placenta, wher ...	2014	25071574
antigen export during liver infection of the malaria parasite augments protective immunity.	protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. intracellular plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class i (mhc-i) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. whether exported liver-stage proteins constitute better candidates for mhc-i antigen presentation to cd8(+) t lymphocytes remains unknown. here, we systematica ...	2014	25073641
in depth annotation of the anopheles gambiae mosquito midgut transcriptome.	genome sequencing of anopheles gambiae was completed more than ten years ago and has accelerated research on malaria transmission. however, annotation needs to be refined and verified experimentally, as most predicted transcripts have been identified by comparative analysis with genomes from other species. the mosquito midgut-the first organ to interact with plasmodium parasites-mounts effective antiplasmodial responses that limit parasite survival and disease transmission. high-throughput illum ...	2014	25073905
maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine borrelia and plasmodium co-infection model.	in the plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. in this study, we investigated the immune responses in balb/c mice, co-infected with plasmodium berghei nk65 parasites and the relapsing fever bacterium borrelia duttonii. in contras ...	2014	25075973
potent antimalarial activity of acriflavine in vitro and in vivo.	malaria continues to be a major health problem globally. there is an urgent need to find new antimalarials. acriflavine (acf) is known as an antibacterial agent and more recently as an anticancer agent. here, we report that acf inhibits the growth of asexual stages of both chloroquine (cq) sensitive and resistant strains of human malarial parasite, plasmodium falciparum in vitro at nanomolar concentration. acf clears the malaria infection in vivo from the bloodstreams of mice infected with plasm ...	2014	25089658
genetic ablation of plasmodj1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production.	malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multistage development in diverse environments. to gain insights into the parasite's stress response mechanisms, we investigated a conserved plasmodium protein, which we have named plasmodj1 on the basis of the presence of a putative cysteine protease motif of the dj-1/pfpi superfamily, for its activities, potential to respond to stresses and role in parasite development. plasmodj1 is expr ...	2014	25091419
interaction between rifampicin, amodiaquine and artemether in mice infected with chloroquine resistant plasmodium berghei.	artemisinin-based combination therapy (act) remains the most effective chemotherapeutic strategy in the management of malaria. however, reports of reduced susceptibility of plasmodium falciparum to the act justify the need for continued search for alternative anti-malarial drugs. the use of antibiotics with anti-malarial properties represents a potentially valuable chemotherapeutic option for the management of drug resistant infections. thus, the intrinsic anti-malarial activity of the combinati ...	2014	25091936
genetic ablation of plasmodj1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production.	malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multistage development in diverse environments. to gain insights into the parasite's stress response mechanisms, we investigated a conserved plasmodium protein, which we have named plasmodj1 on the basis of the presence of a putative cysteine protease motif of the dj-1/pfpi superfamily, for its activities, potential to respond to stresses and role in parasite development. plasmodj1 is expr ...	2014	25097910
expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of plasmodium yoelii.	host cell invasion by apicomplexan parasites marks a crucial step in disease establishment and pathogenesis. the moving junction (mj) is a conserved and essential feature among parasites of this phylum during host cell invasion, thus proteins that associate at this mj are potential targets of drug and vaccine development. in both toxoplasma gondii and plasmodium falciparum, a micronemal protein, apical membrane antigen 1 (ama1), and rhoptry neck proteins (rons; ron2 and ron4) form an essential c ...	2014	25102354
2-octadecynoic acid as a dual life stage inhibitor of plasmodium infections and plasmodial fas-ii enzymes.	the malaria parasite plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (ls) followed by a blood stage with all clinical manifestation of the disease. in this study, we investigated a series of 2-alkynoic fatty acids (2-afas) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-octadecynoic acid (2-oda) was identified as the best inhibitor of plasmodium berghei parasites with ten times higher potency (ic50= ...	2014	25103602
antimalarial activity of the myxobacterial macrolide chlorotonil a.	myxobacteria are gram-negative soil-dwelling bacteria belonging to the phylum proteobacteria. they are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. in the course of a bioactivity screening program of secondary metabolites produced by sorangium cellulosum strains, the macrolide chlorotonil a was found to exhibit promising antimalarial activity. subsequently, we evaluated chlorotonil a against plasmodium falcipar ...	2014	25114138
vectored antibody gene delivery protects against plasmodium falciparum sporozoite challenge in mice.	malaria caused by plasmodium falciparum kills nearly one million children each year and imposes crippling economic burdens on families and nations worldwide. no licensed vaccine exists, but infection can be prevented by antibodies against the circumsporozoite protein (csp), the major surface protein of sporozoites, the form of the parasite injected by mosquitoes. we have used vectored immunoprophylaxis (vip), an adeno-associated virus-based technology, to introduce preformed antibody genes encod ...	2014	25114213
immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates plasmodium infection in mice.	subtilisin-like protease 2 (sub2) is a conserved serine protease utilized by plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. to determine if sub2 is a suitable vaccine target to interfere with malaria parasite development, the effects of sub2-immunization on the plasmodium life cycle were examined in its vertebrate and invertebrate hosts.	2014	25115675
depletion of regulatory t cells augments a vaccine-induced t effector cell response against the liver-stage of malaria but fails to increase memory.	regulatory t cells (t(reg)) have been shown to restrict vaccine-induced t cell responses in different experimental models. in these studies cd4(+)cd25(+) t(reg) were depleted using monoclonal antibodies against cd25, which might also interfere with cd25 on non-regulatory t cell populations and would have no effect on foxp3(+)cd25(-) t(reg). to obtain more insights in the specific function of t(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressi ...	2014	25115805
proteomic analysis of the plasmodium male gamete reveals the key role for glycolysis in flagellar motility.	gametogenesis and fertilization play crucial roles in malaria transmission. while male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. for example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown.	2014	25124718
in vitro and in vivo anti-malarial activity of limonoids isolated from the residual seed biomass from carapa guianensis (andiroba) oil production.	carapa guianensis is a cultivable tree used by traditional health practitioners in the amazon region to treat several diseases and particularly symptoms related to malaria. abundant residual pressed seed material (rpsm) results as a by-product of carapa or andiroba oil production. the objective of this study was to evaluate the in vitro and in vivo anti-malarial activity and cytotoxicity of limonoids isolated from c. guaianensis rpsm.	2014	25124944
anopheles gambiae eicosanoids modulate plasmodium berghei survival from oocyst to salivary gland invasion.	eicosanoids affect the immunity of several pathogen/insect models, but their role on the anopheles gambiae response to plasmodium is still unknown. plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (in), or a substrate, arachidonic acid (aa), at day 7 or day 12 post-infection (p.i.). salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. in promoted infection upon sporozoite release from oocysts, but inhibited infectio ...	2014	25141285
43 kda and 66 kda, two blood stage antigens induce immune response in plasmodium berghei malaria.	the hunt for an effective vaccine against malaria still continues. several new target antigens as candidates for vaccine design are being explored and tested for their efficacy. in the present study the sera from mice immunized with 24,000 x g fraction of plasmodium berghei has been used to identify highly immunogenic blood stage antigens. the protective antibodies present in immune sera were covalently immobilized on cnbr activated sepharose 4b and used for affinity chromatography purification ...	2014	25141540
preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles.	primaquine (pq) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. pq use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing ...	2014	25143734
dominant negative mutant of plasmodium rad51 causes reduced parasite burden in host by abrogating dna double-strand break repair.	malaria parasites survive through repairing a plethora of dna double-stranded breaks (dsbs) experienced during their asexual growth. in plasmodium rad51 mediated homologous recombination (hr) mechanism and homology-independent alternative end-joining mechanism have been identified. here we address whether loss of hr activity can be compensated by other dsb repair mechanisms. creating a transgenic plasmodium line defective in hr function, we demonstrate that hr is the most important dsb repair pa ...	2014	25145341
orally bioavailable 6-chloro-7-methoxy-4(1h)-quinolones efficacious against multiple stages of plasmodium.	the continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. research was initiated to revisit antimalarials developed in the 1940s ...	2014	25148516
evaluation of the adjuvant activity of propranolol, a beta-adrenergic receptor antagonist, on efficacy of a malaria vaccine model in balb/c mice.	we have previously shown the adjuvant activity of propranolol (prp) (a beta-adrenergic receptor antagonist) using a vaccine model for salmonella typhimurium. in this study prp was used as an adjuvant in combination with plasmodium berghei (p. berghei) whole blood stage (pwbs) antigens. balb/c mice were immunized three times with a 2-week interval, either pwbs vaccine alone or in combination with the adjuvant alum or propranolol. the control group received phosphate buffered saline. evaluation of ...	2014	25150071
molecular characterization of calreticulin from anopheles stephensi midgut cells and functional assay of the recombinant calreticulin with plasmodium berghei ookinetes.	transmission blocking vaccines (tbvs) that target the antigens on the midgut epithelium of anopheles mosquitoes are among the promising tools for the elimination of the malaria parasite. characterization and analysis of effective antigens is the first step to design tbvs. calreticulin (crt), a lectin-like protein, from anopheles albimanus midgut, has shown antigenic features, suggesting a promising and novel tbv target. crt is a highly conserved protein with similar features in vertebrates and i ...	2014	25150160
an essential role of the basal body protein sas-6 in plasmodium male gamete development and malaria transmission.	gametocytes are the sole plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. flagellum assembly of the plasmodium male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. the centriole/basal body protein sas-6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ ...	2014	25154861
evaluation of antimalarial activity of leaves of acokanthera schimperi and croton macrostachyus against plasmodium berghei in swiss albino mice.	malaria is one of the most important tropical diseases and the greatest cause of hospitalization and death. recurring problems of drug resistance are reinforcing the need for finding new antimalarial drugs. in this respect, natural plant products are the main sources of biologically active compounds and have potential for the development of novel antimalarial drugs. a study was conducted to evaluate extracts of the leaves of croton macrostachyus and acokanthera schimperi for their in vivo antima ...	2014	25155821
the subcellular location of ovalbumin in plasmodium berghei blood stages influences the magnitude of t-cell responses.	model antigens are frequently introduced into pathogens to study determinants that influence t-cell responses to infections. to address whether an antigen's subcellular location influences the nature and magnitude of antigen-specific t-cell responses, we generated plasmodium berghei parasites expressing the model antigen ovalbumin (ova) either in the parasite cytoplasm or on the parasitophorous vacuole membrane (pvm). for cytosolic expression, ova alone or conjugated to mcherry was expressed fro ...	2014	25156724
damage to the blood-brain barrier during experimental cerebral malaria results from synergistic effects of cd8+ t cells with different specificities.	cd8(+) t cells play a pathogenic role in the development of murine experimental cerebral malaria (ecm) induced by plasmodium berghei anka (pba) infection in c57bl/6 mice. only a limited number of cd8(+) epitopes have been described. here, we report the identification of a new epitope from the bergheilysin protein recognized by pba-specific cd8(+) t cells. induction and functionality of these specific cd8(+) t cells were investigated in parallel with previously reported epitopes, using new tools ...	2014	25156726
in vivo antiplasmodial potentials of the combinations of four nigerian antimalarial plants.	various combinations of nauclea latifolia root, artocarpus altilis stem bark, murraya koenigii leaf and enantia chlorantha stem bark used in african ethnomedicine as decoctions for malaria and fevers, and combinations with standard drugs, were investigated for antiplasmodial activities using plasmodium berghei berghei-infected mice. the respective prophylactic and curative ed50 values of 189.4 and 174.5 mg/kg for n. latifolia and chemosuppressive ed50 value of 227.2 mg/kg for a. altilis showed t ...	2014	25162955
a cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.	plasmodium parasites express a potent inhibitor of cysteine proteases (icp) throughout their life cycle. to analyze the role of icp in different life cycle stages, we generated a stage-specific knockout of the plasmodium berghei icp (pbicp). excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual pbicp protein being detectable in sporozoites. the vast majority of these parasites invading a cultured hepatocyte cell ...	2014	25166051
micromagnetic resonance relaxometry for rapid label-free malaria diagnosis.	we report a new technique for sensitive, quantitative and rapid detection of plasmodium spp.-infected red blood cells (rbcs) by means of magnetic resonance relaxometry (mrr). during the intraerythrocytic cycle, malaria parasites metabolize large amounts of cellular hemoglobin and convert it into hemozoin crystallites. we exploit the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnet ...	2014	25173428
vascular dysfunction as a target for adjuvant therapy in cerebral malaria.	cerebral malaria (cm) is a life-threatening complication of plasmodium falciparum malaria that continues to be a major global health problem. brain vascular dysfunction is a main factor underlying the pathogenesis of cm and can be a target for the development of adjuvant therapies for the disease. vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. in this review, we discuss t ...	2014	25185000
loss of toll-like receptor 7 alters cytokine production and protects against experimental cerebral malaria.	malaria, caused by plasmodium sp. parasites, is a leading cause of global morbidity and mortality. cerebral malaria, characterized by neurological symptoms, is a life-threatening complication of malaria affecting over 500,000 young children in africa every year. because of the prevalence and severity of cerebral malaria, a better understanding of the underlying molecular mechanisms of its pathology is desirable and could inform future development of therapeutics. this study sought to clarify the ...	2014	25192715
plasma micrornas are promising novel biomarkers for the early detection of toxoplasma gondii infection.	micrornas (mirnas) have been shown to be present in plasma, which are remarkably stable, and have been suggested as disease biomarkers. toxoplasma gondii (t. gondii) is a protozoan parasite that is infective to a wide range of animals and human beings. previous studies have found that the parasite generated a large number of mirnas during proliferation and it is known that the spectrum of mirna expression in the infected hosts is pathogen-specific. to date, there are no reports regarding the app ...	2014	25199527
a novel plasmodium-specific prodomain fold regulates the malaria drug target sub1 subtilase.	the plasmodium subtilase sub1 plays a pivotal role during the egress of malaria parasites from host hepatocytes and erythrocytes. here we report the crystal structure of full-length sub1 from the human-infecting parasite plasmodium vivax, revealing a bacterial-like catalytic domain in complex with a plasmodium-specific prodomain. the latter displays a novel architecture with an amino-terminal insertion that functions as a 'belt', embracing the catalytic domain to further stabilize the quaternary ...	2014	25204226
characterization of plasmodium developmental transcriptomes in anopheles gambiae midgut reveals novel regulators of malaria transmission.	the passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. here, we used dna microarrays to profile the developmental transcriptomes of the rodent malaria parasite plasmodium berghei in vivo, in the midgut of anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. data analysis identified several distinct transcriptional programmes en ...	2014	25225164
trpv1 antagonism by capsazepine modulates innate immune response in mice infected with plasmodium berghei anka.	thousands of people suffer from severe malaria every year. the innate immune response plays a determinant role in host's defence to malaria. transient receptor potential vanilloid 1 (trpv1) modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. we investigated the effects of capsazepine, a trpv1 antagonist, in malaria. c57bl/6 mice received 10(5) red blood cells infected with plasmodium berghei anka intraperitoneally. noninfected mi ...	2014	25242870
anopheles gambiae blood feeding initiates an anticipatory defense response to plasmodium berghei.	mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. much remains unknown about how different pathogens are sensed and specific responses triggered. leucine-rich repeat immune proteins (lrims) are a mosquito-specific family of putative innate receptors. although some lrims have been implicated in mosquito immune responses, the function of most family members is largely unknown. we screened anopheles gambiae lrims by rnai for effects on mosquito ...	2014	25247883
zipco, a putative metal ion transporter, is crucial for plasmodium liver-stage development.	the malaria parasite, plasmodium, requires iron for growth, but how it imports iron remains unknown. we characterize here a protein that belongs to the zip (zrt-, irt-like protein) family of metal ion transport proteins and have named zip domain-containing protein (zipco). inactivation of the zipco-encoding gene in plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. iron/zi ...	2014	25257508
distinct properties of the egress-related osmiophilic bodies in male and female gametocytes of the rodent malaria parasite plasmodium berghei.	gametogenesis is the earliest event after uptake of malaria parasites by the mosquito vector, with a decisive impact on colonization of the mosquito midgut. this process is triggered by a drop in temperature and contact with mosquito molecules. in a few minutes, male and female gametocytes escape from the host erythrocyte by rupturing the parasitophorous vacuole and the erythrocyte membranes. electron-dense, oval-shaped organelles, the osmiophilic bodies (ob), have been implicated in the egress ...	2015	25262869
direct evidence for the atovaquone action on the plasmodium cytochrome bc1 complex.	atovaquone, a coenzyme q analogue has been indicated to specifically target the cytochrome bc1 complex of the mitochondrial respiratory chain in the malarial parasite and other protozoan. various mutations in the quinone binding site of the cytochrome b gene of plasmodium spp. such as m133i, l144s, l271v, k272r, y268c, y268s, y268n, and v284f are suggesting to associate with resistance to atovaquone. there is no direct evidence of relation between the mutations and resistance to atovaquone in pl ...	2015	25264100
modulatory effect of crude aqueous extract of lingzhi or reishi medicinal mushroom, ganoderma lucidum (higher basidiomycetes), on hematological and antioxidant indices in plasmodium berghei-infected mice.	hematological and antioxidant effects of the aqueous extract of fruiting bodies of ganoderma lucidum were evaluated in plasmodium berghei-infected mice. extract was administered at doses of 100, 250, and 500 mg/kg body weight by an intragastric tube once daily for 14 d starting from the fourth day after parasite inoculation. at the end of treatment period, mice in each group were sacrificed and blood was collected for hematological and biochemical analyses. a significant (p<0.05) decrease was ob ...	2014	25271985
predictive criteria to study the pathogenesis of malaria-associated ali/ards in mice.	malaria-associated acute lung injury/acute respiratory distress syndrome (ali/ards) often results in morbidity and mortality. murine models to study malaria-associated ali/ards have been described; we still lack a method of distinguishing which mice will develop ali/ards before death. this work aimed to characterize malaria-associated ali/ards in a murine model and to demonstrate the first method to predict whether mice are suffering from ali/ards before death. dba/2 mice infected with plasmodiu ...	2014	25276057
antimalarial activity of malaysian plectranthus amboinicus against plasmodium berghei.	malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of plasmodium. the protozoans have developed resistance against many of current drugs. it is urgent to find an alternative source of new antimalarial agent. in the effort to discover new antimalarial agents, this research has been conducted on plectranthus amboinicus.	2014	25276063
effect of thioredoxin peroxidase-1 gene disruption on the liver stages of the rodent malaria parasite plasmodium berghei.	phenotypic observation of thioredoxin peroxidase-1 (tpx-1) gene-disrupted plasmodium berghei (tpx-1 ko) in the liver-stage was performed with an in vitro infection system in order to investigate defective liver-stage development in a mouse infection model. indirect immunofluorescence microscopy assay with anti-circumsporozoite protein antibody revealed that in the liver schizont stage, tpx-1 ko parasite cells were significantly smaller than cells of the wild-type parent strain (wt). indirect imm ...	2015	25284813
evaluation of the antimalarial potential of icacina senegalensis juss (icacinaceae).	to evaluate in vivo antimalarial activity of methanol leaf extract of icacina senegalensis.	2014	25312169
design, synthesis and evaluation of antimalarial potential of polyphosphazene linked combination therapy of primaquine and dihydroartemisinin.	various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and prim ...	2015	25312346
in vitro activity of waladin benzimidazoles against different life cycle stages of plasmodium parasites.	waladin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from wolbachia endobacteria of filarial nematodes. we report that waladin1 and two derivatives killed blood stage plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μm, respectively). one of these derivatives inhibited gliding motility of plasmodium berghei anka infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic r ...	2014	25313210
medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a softfocus kinase library: part 2.	on the basis of our recent results on a novel series of imidazopyridazine-based antimalarials, we focused on identifying compounds with improved aqueous solubility and herg profile while maintaining metabolic stability and in vitro potency. toward this objective, 41 compounds were synthesized and evaluated for antiplasmodial activity against nf54 (sensitive) and k1 (multidrug resistant) strains of the malaria parasite plasmodium falciparum and evaluated for both aqueous solubility and metabolic ...	2014	25313449
enantiomerically pure amino-alcohol quinolines: in vitro anti-malarial activity in combination with dihydroartemisinin, cytotoxicity and in vivo efficacy in a plasmodium berghei mouse model.	as resistance to marketed anti-malarial drugs continues to spread, the need for new molecules active on plasmodium falciparum-resistant strains grows. pure (s) enantiomers of amino-alcohol quinolines previously displayed a good in vitro anti-malarial activity. therefore, a more thorough assessment of their potential clinical use through a rodent model and an in vitro evaluation of their combination with artemisinin was undertaken.	2014	25319003
spatiotemporal requirements for irf7 in mediating type i ifn-dependent susceptibility to blood-stage plasmodium infection.	type i ifn signaling suppresses splenic t helper 1 (th1) responses during blood-stage plasmodium berghei anka (pba) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. interferon regulatory factor 7 (irf7) is considered to be a master regulator of type i ifn responses. here, we assessed irf7 for its roles during lethal pba infection and nonlethal plasmodium chabaudi chabaudi as (pcas) i ...	2015	25319247
anti-relapse activity of mirincamycin in the plasmodium cynomolgi sporozoite-infected rhesus monkey model.	mirincamycin is a close analog of the drug clindamycin used to treat plasmodium falciparum blood stages. the clinical need to treat plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.	2014	25326032
exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage plasmodium berghei infection.	the thymus plays an important role shaping the t cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. it has been shown that, during plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of cd4+cd8+ double-positive (dp) t cells to the periphery. to investigate whether autoimmune diseases are affected after plasmodium berghei nk65 infection, we immunized c57bl/6 mice, which was previously infected with p. berghei nk ...	2014	25329161
plasmodium berghei histamine-releasing factor favours liver-stage development via inhibition of il-6 production and associates with a severe outcome of disease.	plasmodium spp., which causes malaria, produces a histamine-releasing factor (hrf), an orthologue of mammalian hrf. histamine-releasing factor produced by erythrocytic stages of the parasite is thought to play a role in the pathogenesis of severe malaria. here, we show in a rodent model that hrf is not important during the erythrocytic but pre-erythrocytic phase of infection, which mainly consists in the transformation in the liver of the mosquito-injected parasite form into the erythrocyte-infe ...	2015	25329441
jpc-2997, a new aminomethylphenol with high in vitro and in vivo antimalarial activities against blood stages of plasmodium.	4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(6-(trifluoromethyl)pyridin-3-yl)-phenol (jpc-2997) is a new aminomethylphenol compound that is highly active in vitro against the chloroquine-sensitive d6, the chloroquine-resistant w2, and the multidrug-resistant tm90-c2b plasmodium falciparum lines, with 50% inhibitory concentrations (ic50s) ranging from 7 nm to 34 nm. jpc-2997 is >2,500 times less cytotoxic (ic50s > 35 μm) to human (hepg2 and hek293) and rodent (bhk) cell lines than the d6 parasit ...	2015	25331702
in vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine.	several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. tigecycline, a semi-synthetic derivative of minocycline with a unique and novel mechanism of action, is the first clinically available drug in a new class of glycylcycline antibiotics.	2014	25336038
efficacy of intravenous methylene blue, intravenous artesunate, and their combination in preclinical models of malaria.	intravenous artesunate (iv as) is the present treatment of choice for severe malaria, but development of artemisinin resistance indicates that a further agent will be needed. methylene blue (mb) is an approved human agent for iv and oral use, and is already being investigated for oral treatment of uncomplicated malaria. to initiate investigation of iv mb for severe malaria, the efficacy of iv mb was compared to iv as and to their combination in rat and non-human primate malaria models.	2014	25336091
evaluation of some 1h-pyrazole derivatives as a dual acting antimalarial and anti-leishmanial agents.	the synthesis of a novel series of 1h-pyrazole derivatives was achieved by condensation of pyrazole aldehyde 1 with hydrazine hydrate to give hydrazone 7. on the other hand, cyclization of α,β-unsaturated ketone counterpart 2 using hydrazine hydrate in liquid aliphatic acids rendered compounds 4-6 and hydrazine hydrate in ethanol afforded compound 3. the later was allowed to react with aroyl chloride giving rise to compounds 8, 9. all compounds were tested for their in vivo anti-malarial and in ...	2014	25362601
plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice.	the design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.	2014	25373617
lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations.	to achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. to this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). consequently, any reduction in new infections due to drug treatment ...	2014	25385107
complement c5-deficient mice are protected from seizures in experimental cerebral malaria.	studies have demonstrated that the membrane attack complex (mac) of complement can evoke seizures when injected directly into rodent brain. in the course of studies that examine the role of complement in the development of experimental cerebral malaria (ecm), we observed fewer seizures in mice deficient in c5, a component required for mac formation. to determine if the mac contributed to the tonic-clonic seizures characteristic of ecm, we performed long-term video-electroencephalography (eeg) on ...	2014	25385326
in vivo antimalarial activity and toxicological effects of methanolic extract of cocos nucifera (dwarf red variety) husk fibre.	phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of dwarf red variety of cocos nucifera were evaluated in this study.	2014	25412668
red cells from ferrochelatase-deficient erythropoietic protoporphyria patients are resistant to growth of malarial parasites.	many red cell polymorphisms are a result of selective pressure by the malarial parasite. here, we add another red cell disease to the panoply of erythrocytic changes that give rise to resistance to malaria. erythrocytes from individuals with erythropoietic protoporphyria (epp) have low levels of the final enzyme in the heme biosynthetic pathway, ferrochelatase. cells from these patients are resistant to the growth of plasmodium falciparum malarial parasites. this phenomenon is due to the absence ...	2015	25414439
in vitro alterations do not reflect a requirement for host cell cycle progression during plasmodium liver stage infection.	prior to invading nonreplicative erythrocytes, plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. while normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but i ...	2015	25416236
genome-wide rip-chip analysis of translational repressor-bound mrnas in the plasmodium gametocyte.	following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. during sexual development of plasmodium berghei, a rodent model for human malaria species including p. falciparum, the stability of repressed mrnas requires the translational repressors dozi and cith. when these repressors are absent, plasmodium zygote development and transmission to the ...	2014	25418785
hemozoin induces hepatic inflammation in mice and is differentially associated with liver pathology depending on the plasmodium strain.	malaria is a global disease that clinically affects more than two hundred million people annually. despite the availability of effective antimalarials, mortality rates associated with severe complications are high. hepatopathy is frequently observed in patients with severe malarial disease and its pathogenesis is poorly understood. previously, we observed high amounts of hemozoin or malaria pigment in livers from infected mice. in this study, we investigated whether hemozoin is associated with l ...	2014	25419977
histone methyltransferase inhibitors are orally bioavailable, fast-acting molecules with activity against different species causing malaria in humans.	current antimalarials are under continuous threat due to the relentless development of drug resistance by malaria parasites. we previously reported promising in vitro parasite-killing activity with the histone methyltransferase inhibitor bix-01294 and its analogue tm2-115. here, we further characterize these diaminoquinazolines for in vitro and in vivo efficacy and pharmacokinetic properties to prioritize and direct compound development. bix-01294 and tm2-115 displayed potent in vitro activity, ...	2015	25421480
anti-malarial activity of a polyherbal product (nefang) during early and established plasmodium infection in rodent models.	the emerging resistance of plasmodium species to currently available anti-malarials remains a public health concern, hence the need for new effective, safe and affordable drugs. natural products remain a reliable source of drugs. nefang is a polyherbal anti-malarial of the cameroonian folklore medicine with demonstrated in vitro antiplasmodial and antioxidant activities. it is composed of mangifera indica (bark and leaf), psidium guajava, carica papaya, cymbopogon citratus, citrus sinensis, ocim ...	2014	25421605
evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent.	this study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. compound 1 was able to reduce the in vitro parasite burden, in vitro ...	2015	25431148
the repeat region of the circumsporozoite protein is critical for sporozoite formation and maturation in plasmodium.	the circumsporozoite protein (csp) is the major surface protein of the sporozoite stage of malaria parasites and has multiple functions as the parasite develops and then migrates from the mosquito midgut to the mammalian liver. the overall structure of csp is conserved among plasmodium species, consisting of a species-specific central tandem repeat region flanked by two conserved domains: the nh2-terminus and the thrombospondin repeat (tsr) at the cooh-terminus. although the central repeat regio ...	2014	25438048
piperaquine and lumefantrine resistance in plasmodium berghei anka associated with increased expression of ca2+/h+ antiporter and glutathione associated enzymes.	we investigated the mechanisms of resistance of two antimalarial drugs piperaquine (pq) and lumefantrine (lm) using the rodent parasite plasmodium berghei as a surrogate of the human parasite, plasmodium falciparum. we analyzed the whole coding sequence of plasmodium berghei chloroquine resistance transporter (pbcrt) and plasmodium berghei multidrug resistance gene 1(pbmdr-1) for polymorphisms. these genes are associated with quinoline resistance in plasmodium falciparum. no polymorphic changes ...	2014	25448357
bioactivity-guided isolation of antiplasmodial constituents from conyza sumatrensis (retz.) e.h. walker.	conyza sumatrensis (retz.) e.h. walker (cs) leaves are used for traditional treatment of malaria in cameroon. however, the antimalarial activity of the leaf constituents of this plant is still unexplored. the aim of our investigation was to evaluate the antiplasmodial activity of some bioactive constituents from cs leaves. compounds were isolated from cs leaves and structurally elucidated using extensive spectroscopic analysis. the in vitro antiplasmodial activity of the extracts and pure compou ...	2015	25449289
evidence for the contribution of adult neurogenesis and hippocampal cell death in experimental cerebral malaria cognitive outcome.	cognitive dysfunction is a major sign of cerebral malaria (cm). however, the underlying mechanisms of cm cognitive outcome remain poorly understood. a body of evidence suggests that adult neurogenesis may play a role in learning and memory processes. it has also been reported that these phenomena can be regulated by the immune system. we hypothesized that memory dysfunction in cm results from hippocampal neurogenesis impairment mediated by the deregulated immune response during the acute phase o ...	2015	25451296
themis is required for pathogenesis of cerebral malaria and protection against pulmonary tuberculosis.	we identify an n-ethyl-n-nitrosourea (enu)-induced i23n mutation in the themis protein that causes protection against experimental cerebral malaria (ecm) caused by infection with plasmodium berghei anka. themis(i23n) homozygous mice show reduced cd4(+) and cd8(+) t lymphocyte numbers. ecm resistance in p. berghei anka-infected themis(i23n) mice is associated with decreased cerebral cellular infiltration, retention of blood-brain barrier integrity, and reduced proinflammatory cytokine production. ...	2015	25452553
plasmodium berghei glycine cleavage system t-protein is non-essential for parasite survival in vertebrate and invertebrate hosts.	t-protein, an aminomethyltransferase, represents one of the four components of glycine cleavage system (gcs) and catalyzes the transfer of methylene group from h-protein intermediate to tetrahydrofolate (thf) forming n(5), n(10)-methylene thf (ch2-thf) with the release of ammonia. the malaria parasite genome encodes t-, h- and l-proteins, but not p-protein which is a glycine decarboxylase generating the aminomethylene group. a putative gcs has been considered to be functional in the parasite mit ...	2014	25454081
the plasmodium berghei sexual stage antigen psop12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.	anti-malarial transmission-blocking vaccines (tbvs) aim to inhibit the transmission of plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. there are currently only five lead tbv candidates under examination. there is a consequent need to identify novel antigens to allow the formulation of new potent ...	2015	25454088
antiplasmodial activity of solvent fractions of methanolic root extract of dodonaea angustifolia in plasmodium berghei infected mice.	malaria is one of the most important infectious diseases in the world. the choice for the treatment is highly limited, and several of these may eventually be lost or compromised due to drug resistance. the use of plant medicine in the treatment of malaria and its various presentations is a common practice in many countries of africa where the disease is mostly endemic. dodonaea angustifolia is traditionally used in ethiopia for prophylaxis against malaria. the present study is attempted to evalu ...	2014	25465394
mosquito akirin as a potential antigen for malaria control.	the control of vector-borne diseases is important to improve human and animal health worldwide. malaria is one of the world's deadliest diseases and is caused by protozoan parasites of the genus plasmodium, which are transmitted by anopheles spp. mosquitoes. recent evidences using subolesin (sub) and akirin (akr) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. these experiments suggested the possibi ...	2014	25472895
experimental cerebral malaria pathogenesis--hemodynamics at the blood brain barrier.	cerebral malaria claims the lives of over 600,000 african children every year. to better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, plasmodium berghei anka (pba) infected cba/caj mice, which develop experimental cerebral malaria (ecm), and p. yoelii 17xl (pyxl) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. using a combination of intravital im ...	2014	25474413
plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.	the invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. the pellicle is characterised by a double-layered 'inner membrane complex' (imc) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (spn). the spn consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. here, we re-appraise ...	2014	25475193
formulation of nanotized curcumin and demonstration of its antimalarial efficacy.	the present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria.	2014	25484584
antihemolytic activities of green tea, safflower, and mulberry extracts during plasmodium berghei infection in mice.	malaria-associated hemolysis is associated with mortality in adult patients. it has been speculated that oxidative stress and inflammation induced by malaria parasite are involved in its pathophysiology. hence, we aimed to investigate the antihemolytic effect of green tea, safflower, and mulberry extracts against plasmodium berghei infection. aqueous crude extracts of these plants were prepared using hot water method and used for oral treatment in mice. groups of icr mice were infected with 6 × ...	2014	25485155
pharmacokinetic-pharmacodynamic analysis of spiroindolone analogs and kae609 in a murine malaria model.	limited information is available on the pharmacokinetic (pk) and pharmacodynamic (pd) parameters driving the efficacy of antimalarial drugs. our objective in this study was to determine dose-response relationships of a panel of related spiroindolone analogs and identify the pk-pd index that correlates best with the efficacy of kae609, a selected class representative. the dose-response efficacy studies were conducted in the plasmodium berghei murine malaria model, and the relationship between dos ...	2015	25487807
brine shrimp cytotoxicity and antimalarial activity of plants traditionally used in treatment of malaria in msambweni district.	in kenya, most people use traditional medicine and medicinal plants to treat many diseases including malaria. to manage malaria, new knowledge and products are needed. traditional herbal medicine has constituted a good basis for antimalarial lead discovery and drug development.	2015	25495507
lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by plasmodium berghei anka in balb/c mice.	there is an urgent need to develop and test novel compounds against malaria infection. carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit plasmodium falciparum in vitro. however, they are inflammatory and alter the permeability of the blood-brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (cm), a severe complication of the disease. in this work, the authors look into the effects of the admin ...	2014	25495520
efficacy of intranasal administration of artesunate in experimental cerebral malaria.	improving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier. therefore, it could be helpful and suitable to ...	2014	25516091