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clinical profiles of 13 children with plasmodium vivax cerebral malaria.bikaner region is endemic for both p. vivax and p. falciparum malaria. usually, cerebral malaria is caused by p. falciparum but it has been reported recently also in p. vivax mono-infection. epidemiologic studies and clinical descriptions of p. vivax cerebral malaria in children are rare.201122041470
Flow-induced channel formation in the cytoplasm of motile cells.A model is presented to explain the development of flow channels within the cytoplasm of the plasmodium of the giant amoeba Physarum polycephalum. The formation of channels is related to the development of a self-organizing tubular network in large cells. Experiments indicate that the flow of cytoplasm is involved in the development and organization of these networks, and the mathematical model proposed here is motivated by recent experiments involving the observation of development of flow chan ...201121867307
Thermodynamic concepts in the study of microbial populations: age structure in Plasmodium falciparum infected red blood cells.Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretati ...201122066004
Development and evaluation of a prototype non-woven fabric filter for purification of malaria-infected blood.Many malaria-related studies depend on infected red blood cells (iRBCs) as fundamental material; however, infected blood samples from human or animal models include leukocytes (white blood cells or WBCs), especially difficult to separate from iRBCs in cases involving Plasmodium vivax. These host WBCs are a source of contamination in biology, immunology and molecular biology studies, requiring their removal. Non-woven fabric (NWF) has the ability to adsorb leukocytes and is already used as filtra ...201121867550
Emerging functions of transcription factors in malaria parasite.Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs) are either associated directly with RNA polymerase or add in bui ...201122131806
"Bird biting" mosquitoes and human disease: a review of the role of Culex pipiens complex mosquitoes in epidemiology.The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Culex pipiens pipi ...201121875691
"Wonders unconceived": reflections on the birth of medical entomology.Prior to Patrick Manson's discovery in 1877 that the mosquito Culex fatigans was the intermediate host of filariasis, the association of insects with disease and the nature of disease transmission was almost entirely speculation. Manson's work was incomplete, however, because it showed the manner in which the mosquito acquired the infection from humans, but failed to show the way in which the mosquito passed the infection to humans. That pathogens were transmitted by the bite of an infected fema ...201121857128
Trials for the co-expression of the merozoite surface protein-1 and circumsporozoite protein genes of Plasmodium vivax.Merozoite surface protein-1 (MSP-1), a major asexual blood stage antigen, and circumsporozoite protein (CSP), a component of sporozoites that includes a Plasmodium vivax B-cell epitope, are strong candidates for use in a malaria vaccine. A chimeric recombinant gene containing portions of both msp-1 and csp from P. vivax separated by Pro-Gly linker motif was generated. The construct gene was named mlc (msp-1, linker, and csp). The MLC chimeric recombinant protein had a molecular weight of approxi ...201121907198
the plasmodium falciparum malaria m1 alanyl aminopeptidase (pfa-m1): insights of catalytic mechanism and function from md simulations.malaria caused by several species of plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. the widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. while the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins. the p. falciparum malarial m1 alanyl-aminope ...201122205955
Design and synthesis of new N-(5-trifluoromethyl)-1H-1,2,4-triazol-3-yl benzenesulfonamides as possible antimalarial prototypes.A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, ¹H-, ¹³C-, ¹?F-NMR, MS and elemental analysis. A docking study based on sulfonamides previously used against malaria identified trifluoromethyl-substituted derivatives to be the best lead compounds for new antimalarial ...201121934646
Vaccines against malaria.There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologi ...201121893544
Plasmodium falciparum inhibitor 3 homolog increases protein phosphatase type 1 activity and is essential for parasitic survival.Growing evidence indicates that the protein regulators governing protein phosphatase 1 (PP1) activity have crucial functions since their deletion drastically affects cell growth and division. PP1 has been found to be essential in Plasmodium falciparum, but little is known about its regulators. In this study, we have identified a homolog of Inhibitor-3 of PP1, named PfI3. Nuclear Magnetic Resonance Spectroscopy (NMR) analysis shows that PfI3 belongs to the disordered protein family. High affinity ...201122128182
Plasmodium falciparum: effect of antimalarial drugs, malaria pigment (ß-haematin) and Plasmodium falciparum lysate on monocyte GTP-cyclohydrolase 1 gene expression.In interferon-? activated human macrophages, GTP-cyclohydrolase 1 catalyses the conversion of guanosine triphosphate to 7,8-dihydroneopterin triphosphate, which is dephosphorylated and oxidized to form neopterin. Elevated levels of neopterin have been detected in the urine and serum of malaria-infected patients. In this study, U937 cells were treated with interferon-? and one of the following antimalarial drugs: amodiaquine, artemisinin, chloroquine, doxycycline, primaquine, pyrimethamine or qui ...201121854775
In vitro antibacterial and antimalarial activity of dehydrophenylalanine-containing undecapeptides alone and in combination with drugs.A set of three cationic undecapeptides, analogous to the previously reported peptide VS2 (KW?FWK?FVK?FVK), was created by alanine substitution in order to probe the effect of hydrophobicity on peptide activity. The activities of these peptides were determined against Escherichia coli, Staphylococcus aureus and the malaria parasite Plasmodium falciparum. VA1, the closest analogue of VS2, showed five-fold augmented activity [minimum inhibitory concentration (MIC)=10µM] against the Gram-positive ba ...201122118799
malaria vaccine cuts risk in half in late-stage trial. 201122064398
epidemiology and control of malaria in colombia.malaria is currently one of the most serious public health problems in colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to plasmodium falciparum. a limited number of severe and complicated cases have resulted in mortality, which is a downward trend that h ...201121881765
Ultrastructural and real-time microscopic changes in P. falciparum-infected red blood cells following treatment with antimalarial drugs.Ultrastructural changes to P. falciparum-infected red blood cells were examined in vitro after treatment with antimalarial drugs. Artesunate had the most rapid parasitocidal effect. All three drugs caused structural changes within the parasite, including dilatation of the parasitophorus vacuole membrane, depletion of ribosomes, mitochondrial swelling, and decreased formation of hemozoin crystals. The structure of surface knobs and Maurer's clefts were similar to controls but reduced in number. O ...201121910567
digestive vacuoles of plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes.sequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe plasmodium falciparum malaria. a link between these events emerged through the discovery that the parasite digestive vacuole (dv), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. complement attack occurs exclusively on the membrane of the dvs, and the question followed wh ...201121911835
malaria-infected mice are completely cured by one 6 mg/kg oral dose of a new monomeric trioxane sulfide combined with mefloquine.sixteen new anilide derivatives of the natural trioxane artemisinin were prepared and evaluated for antimalarial efficacy in plasmodium berghei infected mice. of these 16 new anilides administered orally as one 6 mg/kg dose combined with 18 mg/kg mefloquine hydrochloride, only sulfide 3-artesanilide 12d was completely curative: on day 30 after infection, all mice in this group had no detectable parasitemia, gained as much weight as the uninfected control mice, and behaved normally.201122128829
Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine.Molecular markers for surveillance of Plasmodium falciparum resistance to current antimalarials are sorely needed. A 28-day efficacy study of artemether-lumefantrine in eastern Sudan identified 5 treatment failures among 100 evaluable patients; 9 further individuals were parasite positive by PCR during follow-up. Polymorphisms in pfatpase6 and pfmdr1 were evaluated by DNA sequencing. One individual carried parasites with a novel pfmdr1 polymorphism (F1044L). pfmdr1 gene amplification in parasite ...201121896916
[Therapeutic management of malaria.]Plasmodium falciparum and to some extent malaria caused by other species of Plasmodia can quickly lead to cerebral malaria, acute renal failure, or acute respiratory distress syndrome. The mortality rate for patients with severe malaria lies around 10%. Malaria must be given priority in the differential diagnosis of travelers returning febrile from endemic areas. Treatment requires prompt administration of safe and fast-acting antimalarials, which in severe malaria is treatment with quinine or a ...201122071912
Infection dynamics of endemic malaria in a wild bird population: parasite species-dependent drivers of spatial and temporal variation in transmission rates.1. Investigating the ecological context in which host-parasite interactions occur and the roles of biotic and abiotic factors in forcing infection dynamics is essential to understanding disease transmission, spread and maintenance. 2. Despite their prominence as model host-pathogen systems, the relative influence of environmental heterogeneity and host characteristics in influencing the infection dynamics of avian blood parasites has rarely been assessed in the wild, particularly at a within-pop ...201121848864
Determinants of relapse periodicity in Plasmodium vivax malaria.ABSTRACT: Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the s ...201121989376
a novel piezoelectric immunosensor for the detection of malarial plasmodium falciparum histidine rich protein-2 antigen.a novel piezoelectric (pz) immunosensor for the direct detection of malarial plasmodium falciparum histidine rich protein-2 (pfhrp-2) antigen was developed. the mixed self-assembled monolayers (sams) of thioctic acid and 1-dodecanethiol were formed on gold surface of quartz crystal. cyclic voltammetry, electrochemical impedance spectroscopy and surface raman spectroscopy techniques were used to characterize the mixed sams. the rabbit anti-pfhrp-2 antibodies were coupled on mixed sam modified gol ...201121872024
wolbachia strain walbb enhances infection by the rodent malaria parasite plasmodium berghei in anopheles gambiae mosquitoes.wolbachia, a common bacterial endosymbiont of insects, has been shown to protect its hosts against a wide range of pathogens. however, not all strains exert a protective phenotype on their host. here we assess the affect of two divergent wolbachia strains, walbb from aedes albopticus and wmelpop from drosophila melanogaster, on the vector competence of anopheles gambiae challenged with plasmodium berghei. we show the walbb strain significantly increases p. berghei oocyst levels in the mosquito m ...201122210220
Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum.Having previously characterized chloroquine (CQ)-induced programmed cell death (PCD) hallmarks in the malaria parasite Plasmodium falciparum and delineating a pathway linking these features, the roles of non-classical mediators were investigated in this paper. It was shown that the later stages of this pathway are Ca(2+)-dependent and transcriptionally regulated. Moreover, it was demonstrated for the first time that micromolar concentrations of CQ partially permeabilized the parasite's digestive ...201121993392
3d structure and immunogenicity of plasmodium falciparum sporozoite induced associated protein peptides as components of fully-protective anti-malarial vaccine.siap-1 and siap-2 are proteins which are implicated in early events involving plasmodium falciparum infection of the anopheles mosquito vector and the human host. high affinity hela and hepg2 cell binding conserved peptides have been previously identified in these proteins, i.e. siap-1 34893 ((421)kvqglsyllrrkngtkhpvy(440)) and siap-1 34899 ((541)yvlnskllnsrsfdkfkwiq(560)) and siap-2 36879 ((181)lllystnsednldisfgelq(200)). when amino acid sequences have been properly modified (replacements shown ...201122115782
development and evaluation of a rapid diagnostic test for plasmodium falciparum, p. vivax, and mixed-species malaria antigens.plasmodium falciparum and p. vivax malaria are endemic to many parts of the world and humans can be co-infected with both species. because each plasmodium species has different biological and clinical characteristics, accurate differentiation of the infecting species is essential for effective treatment. therefore, we produced three monoclonal antibodies that recognize the lactate dehydrogenase of p. falciparum, p. vivax, or both to develop the first p. falciparum, p. vivax, and mixed-species in ...201122144432
The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.Plasmodium infection increases the oxidative stress inside the mosquito, leading to a significant alteration on transcription of Anopheles gambiae detoxification genes. Among these detoxification genes several P450 cytochromes and tubulins were differently expressed, suggesting their involvement in the mosquito's response to parasite invasion. P450 cytochromes are usually involved in the metabolism and detoxification of several compounds, but are also regulated by several pathogens, including ma ...201121912622
Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1).Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1) and examine its antigeni ...201122024312
binding and inhibition of human spermidine synthase by decarboxylated s-adenosylhomocysteine.aminopropyltransferases are essential enzymes that form polyamines in eukaryotic and most prokaryotic cells. spermidine synthase (spds) is one of the most well-studied enzymes in this biosynthetic pathway. the enzyme uses decarboxylated s-adenosylmethionine and a short-chain polyamine (putrescine) to make a medium-chain polyamine (spermidine) and 5'-deoxy-5'-methylthioadenosine as a byproduct. here, we report a new spermidine synthase inhibitor, decarboxylated s-adenosylhomocysteine (dcsah). the ...201121898642
longevity and composition of cellular immune responses following experimental plasmodium falciparum malaria infection in humans.cellular responses to plasmodium falciparum parasites, in particular interferon-gamma (ifnγ) production, play an important role in anti-malarial immunity. however, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. here we assess the longevity and composition of cellular immune responses following experimental malar ...201122144890
comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine.dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. we investigated the reactivity of a series of potent amide functionalized tetraoxanes with fe(ii)gluconate, feso(4), feso(4)/tempo, feso(4)/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-triox ...201121888440
design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent.resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. the cysteine protease falcipain-2 (fp-2) and dihydrofolate reductase (dhfr) play crucial roles in the plasmodium life cycle. in this study, a series of first-gereration small molecular dual inhibitor of fp-2 and dhfr hav ...201122192590
treatment guided by rapid diagnostic tests for malaria in tanzanian children: safety and alternative bacterial diagnoses.who guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (rdt). however, there is limited evidence of the safety of this policy in routine outpatient settings in africa.201121978238
genetic control of susceptibility to infection with plasmodium chabaudi chabaudi as in inbred mouse strains.to identify genetic effects modulating the blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to plasmodium chabaudi chabaudi as infection (peak parasitemia, survival). a broad spectrum of responses was observed, with strains such as c57bl/6j being the most resistant (low parasitemia, 100% survival) and strains such as nzw/lacj and c3heb/fej being extremely susceptible (very high parasitemia and uniform lethality). a number of st ...201121975430
structure of the catalytic domain of plasmodium falciparum arf gtpase-activating protein (arfgap).the crystal structure of the catalytic domain of the adp ribosylation factor gtpase-activating protein (arfgap) from plasmodium falciparum has been determined and refined to 2.4 å resolution. multiwavength anomalous diffraction (mad) data were collected utilizing the zn(2+) ion bound at the zinc-finger domain and were used to solve the structure. the overall structure of the domain is similar to those of mammalian arfgaps. however, several amino-acid residues in the area where gap interacts with ...201122102228
The evolution of pyrimethamine resistant dhfr in Plasmodium falciparum of south-eastern Tanzania: comparing selection under SP alone vs SP+artesunate combination.Sulphadoxine-pyrimethamine (SP) resistance is now widespread throughout east and southern Africa and artemisinin compounds in combination with synthetic drugs (ACT) are recommended as replacement treatments by the World Health Organization (WHO). As well as high cure rates, ACT has been shown to slow the development of resistance to the partner drug in areas of low to moderate transmission. This study looked for evidence of protection of the partner drug in a high transmission African context. T ...201122029848
Environmental, entomological, socioeconomic and behavioural risk factors for malaria attacks in Amerindian children of Camopi, French Guiana.Malaria is a major health issue in French Guiana. Amerindian communities remain the most affected. A previous study in Camopi highlighted the predominant role of environmental factors in the occurrence of malaria. However, all parameters involved in the transmission were not clearly identified. A new survey was conducted in order to clarify the risk factors for the presence of malaria cases in Camopi.201121861885
Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand.Resistance to chloroquine is a public health problem worldwide. Polymorphisms of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes have been linked to chloroquine resistance. Although the K76T mutation in the pfcrt gene has been shown to be a key determinant in chloroquine resistance, evidence suggests that the pfmdr1 gene could modulate the level of chloroquine resistance. However, few studies of field isolates could ide ...201121976558
effectiveness of acts in cases of resistance to partner drugs. 201121700240
artemisinin-based combination therapy for treating uncomplicated plasmodium vivax malaria.plasmodium vivax is an important cause of malaria in many parts of asia and south america, and resistance to the standard treatment (chloroquine) is now high in some parts of oceania. this review aims to assess the current treatment options in the light of rising chloroquine resistance.201121735431
plasmodium falciparum malaria endemicity in indonesia in 2010.malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. we used model based geostatistics (mbg) techniques to generate a contemporary map of plasmodium falciparum malaria risk in indonesia in 2010.201121738634
structural basis for the functional and inhibitory mechanisms of +¦-hydroxyacyl-acyl carrier protein dehydratase (fabz) of plasmodium falciparum.the +¦-hydroxyacyl-acyl carrier protein dehydratase of plasmodium falciparum (pffabz) catalyzes the third and important reaction of the fatty acid elongation cycle. the crystal structure of pffabz is available in hexameric (active) and dimeric (inactive) forms. however, pffabz has not been crystallized with any bound inhibitors until now. we have designed a new condition to crystallize pffabz with its inhibitors bound in the active site, and determined the crystal structures of four of these com ...201121843645
design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes.abstract:201121718533
malaria caused by plasmodium vivax complicated by acalculous cholecystitis.we report the first adult cases of acute acalculous cholecystitis (aac) exclusively caused by infections with plasmodium vivax. we reviewed the previous cases of aac occurring during malaria, compared and contrasted the variables of previously reported cases with the cases reported here, examined the pathogenic link between malaria and aac, and considered the diagnostic pitfalls and treatment implications as they applied to clinical outcomes in patients with this serious and potentially underrec ...201121734122
characterization of two malaria parasite organelle translation elongation factor g proteins: the likely targets of the anti-malarial fusidic acid.malaria parasites harbour two organelles with bacteria-like metabolic processes that are the targets of many anti-bacterial drugs. one such drug is fusidic acid, which inhibits the translation component elongation factor g. the response of p. falciparum to fusidic acid was characterised using extended sybr-green based drug trials. this revealed that fusidic acid kills in vitro cultured p. falciparum parasites by immediately blocking parasite development. two bacterial-type protein translation el ...201121695207
application of in-situ hybridization for the detection and identification of avian malaria parasites in paraffin wax-embedded tissues from captive penguins.in captive penguins, avian malaria due to plasmodium parasites is a well-recognized disease problem as these protozoa may cause severe losses among valuable collections of zoo birds. in blood films from naturally infected birds, identification and differentiation of malaria parasites based on morphological criteria are difficult because parasitaemia is frequently light and blood stages, which are necessary for identification of parasites, are often absent. post-mortem diagnosis by histological e ...201121711191
imported malaria in scotland--an overview of surveillance, reporting and trends.imported malaria cases continue to occur and are often underreported. this study assessed reporting of malaria cases and their characteristics in scotland.201122056775
New antimalarial indolone-N-oxides, generating radical species, destabilize the host cell membrane at early stages of Plasmodium falciparum growth: role of band 3 tyrosine phosphorylation.Although indolone-N-oxide (INODs) genereting long-lived radicals possess antiplasmodial activity in the low-nanomolar range, little is known about their mechanism of action. To explore the molecular basis of INOD activity, we screened for changes in INOD-treated malaria-infected erythrocytes (Pf-RBCs) using a proteomics approach. At early parasite maturation stages, treatment with INODs at their IC(50) concentrations induced a marked tyrosine phosphorylation of the erythrocyte membrane protein b ...201122142474
a toolbox to study liver stage malaria.the first obligatory phase of mammalian infection by plasmodium parasites, the causative agents of malaria, occurs in the liver of the host. this stage of plasmodium infection bears enormous potential for anti-malarial intervention. recent technological progress has strongly contributed to overcoming some of the long-standing difficulties in experimentally assessing hepatic infection by plasmodium. here, we review appropriate infection models and infection assessment tools, and provide a compreh ...201122015112
structure and reaction mechanism of phosphoethanolamine methyltransferase from the malaria parasite plasmodium falciparum: an antiparasitic drug target.in the malarial parasite plasmodium falciparum, a multifunctional phosphoethanolamine methyltransferase (pfpmt) catalyzes the methylation of phosphoethanolamine (pea) to phosphocholine for membrane biogenesis. this pathway is also found in plant and nematodes, but pmt from these organisms use multiple methyltransferase domains for the s-adenosylmethionine (adomet) reactions. because pfpmt is essential for normal growth and survival of plasmodium and is not found in humans, it is an antiparasitic ...201122117061
plasmodium falciparum: differential selection of drug resistance alleles in contiguous urban and peri-urban areas of brazzaville, republic of congo.the african continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. we studied the impact of the degree of urbanization on the population genetics of plasmodium falciparum in urban and peri-urban areas in and around the city of brazzaville, republic of congo. this field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows t ...201121858115
clinical and prognostic features among children with acute encephalitis syndrome in nepal; a retrospective study.acute encephalitis syndrome (aes) is commonly seen among hospitalized nepali children. japanese encephalitis (je) accounts for approximately one-quarter of cases. although poor prognostic features for je have been identified, and guide management, relatively little is reported on the remaining three-quarters of aes cases.201122035278
plasmodium falciparum stevor proteins impact erythrocyte mechanical properties.infection of erythrocytes with the human malaria parasite, plasmodium falciparum, results in dramatic changes to the host cell structure and morphology. the predicted functional localization of the stevor proteins at the erythrocyte surface suggests that they may be involved in parasite-induced modifications of the erythrocyte membrane during parasite development. to address the biologic function of stevor proteins, we subjected a panel of stevor transgenic parasites and wild-type clonal lines e ...201122106347
polymorphisms of molecular markers of antimalarial drug resistance and relationship with artesunate-mefloquine combination therapy in patients with uncomplicated plasmodium falciparum malaria in thailand.the aim of this study was to investigate the association between genetic polymorphisms of plasmodium falciparum chloroquine resistance transporter (pfcrt), p. falciparum multidrug resistance 1 (pfmdr1), and p. falciparum atpase (pfatp6) and clinical outcome after a three-day mefloquine-artesunate combination therapy in 134 patients with uncomplicated plasmodium falciparum malaria in an area with multidrug resistance along the thailand-myanmar border. analysis of gene mutation and amplification w ...201121896824
challenges in antimalarial drug discovery.malaria is one of the most devastating diseases in the world, affecting almost 225 million people a year, and causing over 780,000 deaths, most of which are children under the age of 5 years. following the recent call for the eradication of the disease, supported by the who, there has been increasing investment into antimalarial drug-discovery projects. these activities are aimed at generating the next generation of molecules focused on the treatment and transmission-blocking of plasmodium falci ...201121879844
nuclear magnetic resonance: a tool for malaria diagnosis?malaria control can be improved by rapid, sensitive, low-cost detection of infection. several such strategies are being pursued. rapid diagnostic tests can detect infections at parasite densities above 200 μl(-1). polymerase chain reaction methods can detect low parasite densities, but are slow and prone to contamination under field conditions. methods that detect hemozoin presence in blood have been proposed as alternatives for rapid detection of infection. in this study, we used a benchtop nuc ...201122049032
synthesis and antimalarial evaluation of novel isocryptolepine derivatives.a series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3d7) and resistant (w2mef) plasmodium falciparum and for cytotoxicity (3t3 cells). di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (ic(50)=9005 nm) to antimalarial activity (ic(50)=85 nm)). our evaluation of novel ...201122055713
chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage plasmodium falciparum.plasmodium spp parasites harbor an unusual plastid organelle called the apicoplast. due to its prokaryotic origin and essential function, the apicoplast is a key target for development of new anti-malarials. over 500 proteins are predicted to localize to this organelle and several prokaryotic biochemical pathways have been annotated, yet the essential role of the apicoplast during human infection remains a mystery. previous work showed that treatment with fosmidomycin, an inhibitor of non-mevalo ...201121912516
Coinfection of schistosoma (trematoda) with bacteria, protozoa and helminths.This review examines coinfection of selected species of Schistosoma with bacteria, protozoa and helminths and focuses on the effects of the coinfection on the hosts. The review is based mainly on tables that contain the salient information on the coinfecting organisms in vertebrate hosts. Further explanation and clarification of the tables are given in the text. A table is also provided that gives synoptic information on the 37 species in the 19 genera considered in this review. Coinfection stud ...201122137582
performance characteristics of combinations of host biomarkers to identify women with occult placental malaria: a case-control study from malawi.because of its propensity to sequester in the placental intervillous space, plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (pm). we evaluated host biomarkers as potential indicators of occult pm infections.201122174834
A binary ant colony optimization classifier for molecular activities.Chemical fingerprints encode the presence or absence of molecular features and are available in many large databases. Using a variation of the Ant Colony Optimization (ACO) paradigm, we describe a binary classifier based on feature selection from fingerprints. We discuss the algorithm and possible cross-validation procedures. As a real-world example, we use our algorithm to analyze a Plasmodium falciparum inhibition assay and contrast its performance with other machine learning paradigms in use ...201121854036
can wolbachia be used to control malaria?malaria is a mosquito-borne infectious disease caused by plasmodium parasites transmitted by the infectious bite of anopheles mosquitoes. vector control of malaria has predominantly focused on targeting the adult mosquito through insecticides and bed nets. however, current vector control methods are often not sustainable for long periods so alternative methods are needed. a novel biocontrol approach for mosquito-borne diseases has recently been proposed, it uses maternally inherited endosymbioti ...201121881776
Identification of new antimalarial leads by use of virtual screening against cytochrome bc1.Cytochrome bc(1) is a validated drug target in malaria parasites. The spread of Plasmodium falciparum strains resistant to multiple antimalarials emphasizes the urgent need for new drugs. We screened in silico the ZINC and MOE databases, using ligand- and structure-based approaches, to identify new leads for development. The most active compound presented an IC(50) value against cultured P. falciparum of 2 µM and a docking pose consistent with its activity.201121958736
Host and habitat specialization of avian malaria in Africa.Studies of both vertebrates and invertebrates have suggested that specialists, as compared to generalists, are likely to suffer more serious declines in response to environmental change. Less is known about the effects of environmental conditions on specialist versus generalist parasites. Here, we study the evolutionary strategies of malaria parasites (Plasmodium spp.) among different bird host communities. We determined the parasite diversity and prevalence of avian malaria in three bird commun ...201122142265
Regulating the Adaptive Immune Response to Blood-Stage Malaria: Role of Dendritic Cells and CD4Foxp3 Regulatory T Cells.Although a clearer understanding of the underlying mechanisms involved in protection and immunopathology during blood-stage malaria has emerged, the mechanisms involved in regulating the adaptive immune response especially those required to maintain a balance between beneficial and deleterious responses remain unclear. Recent evidence suggests the importance of CD11c(+) dendritic cells (DC) and CD4(+)Foxp3(+) regulatory T cells in regulating immune responses during infection and autoimmune disea ...201122110383
Transgenic Plasmodium parasites stably expressing Plasmodium vivax dihydrofolate reductase-thymidylate synthase as in vitro and in vivo models for antifolate screening.Plasmodium vivax is the most prevalent cause of human malaria in tropical regions outside the African continent. The lack of a routine continuous in vitro culture of this parasite makes it difficult to develop specific drugs for this disease. To facilitate the development of anti-P. vivax drugs, bacterial and yeast surrogate models expressing the validated P. vivax target dihydrofolate reductase-thymidylate synthase (DHFR-TS) have been generated; however, they can only be used as primary screeni ...201121981896
Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study.Sulfadoxine-pyrimethamine (SP) has been widely deployed in Africa for malaria control and molecular evidence of parasite drug-resistance is prevalent. However, the temporal effects on the selection of Plasmodium falciparum are not well understood. We conducted a retrospective serial cross-sectional study between 1997 and 2006 to investigate changes in drug-resistant malaria among pregnant women delivering at a single hospital in Blantyre, Malawi. P. falciparum parasites were genotyped for parasi ...201122119749
[resistance of plasmodium falciparum to antimalarial drugs: impact on malaria pre-elimination in madagascar].the purpose of this review was to provide up-to-date information on the resistance of plasmodium falciparum to the main antimalarials used in madagascar and to assist implementation of the malaria control and elimination program. in 2006, the failure rate for chloroquine treatment was 44% (n = 300) and was comparable to the rate observed in continental africa. most treatment failures occurred after the first week of follow-up. p. falciparum resistance to chloroquine appeared to be special in mad ...201121870564
risk factors for plasmodium falciparum hyperparasitaemia in malarious children.hyperparasitaemia is a feature of childhood severe malaria but there is little information on the risk factors for hyperparasitaemia in malarious children201121982211
evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.in sub-saharan africa, hiv-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, mycobacterium tuberculosis and malaria parasites. the consequences are often devastating, resulting in enhanced morbidity and mortality. due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (siv)-malaria coinfection. in sub-saharan africa, plasmodium falcipa ...201121917966
branch point identification and sequence requirements for intron splicing in plasmodium falciparum.splicing of mrna is an ancient and evolutionarily conserved process in eukaryotic organisms, but intron-exon structures vary. plasmodium falciparum has an extreme at nucleotide bias (>80%), providing a unique opportunity to investigate how evolutionary forces have acted on intron structures. in this study, we developed an in vivo luciferase reporter splicing assay and employed it in combination with lariat isolation and sequencing to characterize 5' and 3' splicing requirements and experimentall ...201121926333
Worldwide incidence of malaria in 2009: estimates, time trends, and a critique of methods.Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries. Here we present a critique of both methods, illustrated with national incidence estimates for 2009.201122205883
Diagnosis of malaria parasitemia in children using a rapid diagnostic test.This cross-sectional study was conducted to evaluate the diagnostic performance of a new rapid immunochromatographic test named "Paracheck pf" in the diagnosis of malaria in Nigerian children.201121860139
Antibody response to allelic variants of 19kDa fragment of MSP-1: Recognition of a variant and protection associated with ethnicity in Assam, India.Evidence suggests association of anti MSP-1(19) antibodies with protection from clinical malaria. However, the target epitope was reported to vary with respect to response to conserved or variant epitopes in different studies. We have investigated here humoral response of naturally exposed individuals of Tibeto-Burman and Austro-Asiatic ethnic groups to E-TSR and Q-KNG variants of MSP-1(19) in comparison to whole merozoite extract (WME) of local strain of Plasmodium falciparum in a longitudinal ...201122133506
febrifugine analogue compounds: synthesis and antimalarial evaluation.febrifugine is an alkaloid isolated from dichroa febrifuga lour as the active component against plasmodium falciparum, but exhibits toxic side effects. in this study novel febrifugine analogues were designed and efficiently synthesized. new compounds underwent efficacy and toxicity evaluation. some compounds are much less toxic than the natural product febrifugine and existing antimalarial drugs and are expected to possess wide therapeutic windows. in aotus monkeys infected with the chloroquine ...201122182577
[nested pcr for malaria detection and plasmodium species identification].according to the sequences of small subunit ribosomal rna (ssu rrna) gene of plasmodium spp., universal and species-specific primers were designed to detect malaria and identify species. 60 blood samples were detected by the established nested pcr method. the results were compared with those of microscopic examination. 40 blood samples were plasmodium-positive by nested pcr with 22 samples of p. falciparum, 13 of p. vivas, 3 with p. falciparum and p. vivax mixed infection, 1 of p. ovale and 1 of ...201121972599
prevalence and density-related concordance of three diagnostic tests for malaria in a region of tanzania with hypoendemic malaria.accurate malaria diagnosis has dual roles in identification of symptomatic persons for effective malaria treatment and also enumeration of asymptomatic persons who contribute to the epidemiologic determinants of transmission. three currently used diagnostic tests, microscopy, rapid diagnostic tests (rdts), and real-time pcr, all have different sensitivities and specificities, which are parasite density dependent. here, we compare their concordance among 451 febrile episodes in a cohort of 2,058 ...201121880972
[rapid malaria tests--good complement to microscopy. high sensitivity for plasmodium falciparum in swedish travellers]. 201122165534
Larvicidal and pupicidal activity of spinosad against the malarial vector Anopheles stephensi.To investigate the larvicidal and pupicidal activity of spinosad against Anopheles stephensi Listen.201121914537
Plasmodium falciparum MLH is schizont stage specific endonuclease.Malaria is one of the most important infectious diseases in many regions around the world including India. Plasmodium falciparum is the cause of most lethal form of malaria while Plasmodium vivax is the major cause outside Africa. Regardless of considerable efforts over the last many years there is still no commercial vaccine against malaria and the disease is mainly treated using a range of established drugs. With time, the malaria parasite is developing drug resistance to most of the commonly ...201122079692
A scalable pipeline for highly effective genetic modification of a malaria parasite.In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Re ...201122020067
stage-specific depletion of myosin a supports an essential role in motility of malarial ookinetes.functional analysis of plasmodium genes by classical reverse genetics is currently limited to mutants that are viable during erythrocytic schizogony, the pathogenic phase of the malaria parasite where transfection is performed. here, we describe a conceptually simple experimental approach to study the function of genes essential to the asexual blood stages in a subsequent life cycle stage by a promoter-swap approach. as a proof of concept we targeted the unconventional class xiv myosin myoa, whi ...201121899701
malaria-related anaemia: a latin american perspective.malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. it mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. although the contribution of the american continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. on the african conti ...201121881762
[advances in research of dihydroartemisinin against parasitic diseases].dihydroartemisinin, the main metabolite of artemisinin and two artemisinin derivatives, artemether and artesunate, is a broad-spectrum anti-parasitic drug. the present paper systematically reviews the advances in research of dihydroartemisinin against plasmodium, schistosoma, pneumocystis, toxoplasma, trichomonas vaginalis, leishmania, giardia lamblia.201122164870
shotgun isotope array for rapid, substrate-specific detection of microorganisms in a microbial community.the shotgun isotope array method has been proposed to be an effective new tool for use in substrate-specific microbe exploration without any prior knowledge of the community composition. proof of concept was demonstrated by detection of acetate-degrading microorganisms in activated sludge and further verified by independent stable isotope probing (sip).201121873478
biomarkers for susceptibility to infection and disease severity in human malaria.malaria remains a major infectious disease that affects millions of people. once infected with plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. although most promising markers are ...201121881759
a head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in african children: a randomized trial.artemisinin-based combination therapies (acts) are the mainstay for the management of uncomplicated malaria cases. however, up-to-date data able to assist sub-saharan african countries formulating appropriate antimalarial drug policies are scarce.201122087077
A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon.Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003.201122004584
Optimization of propafenone analogues as antimalarial leads.Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum. While the drug's potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogues was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 ...201121955244
Vivax malaria in Mauritania includes infection of a Duffy-negative individual.ABSTRACT:201122050867
Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors.ABSTRACT: Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusiv ...201122151840
standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator.a significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (act), signaled emergent artemisinin resistance in western cambodia. accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in plasmodium falciparum. the slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-ma ...201122074219
a single injection of 19 kda carboxy-terminal fragment of plasmodium yoelii merozoite surface protein 1 (pymsp1(19)) formulated with montanide isa and cpg odn induces protective immune response in mice.to investigate the efficacy of a vaccine formulation of the 19 kda conserved carboxyl-terminal fragment of plasmodium yoelii merozoite surface protein-1 (pymsp1(19)) formulated with cpg odn 1826 and montanide isa51 or isa720 when used to immunize mice by a single injection.201122053595
experimentally controlled downregulation of the histone chaperone fact in plasmodium berghei reveals that it is critical to male gamete fertility.human fact (facilitates chromatin transcription) consists of the proteins spt16 and ssrp1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and dna replication. we identified a plasmodium berghei protein, termed fact-l, with homology to the spt16 subunit of fact. epitope tagging of fact-l showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. the gene encoding fact-l could not be dele ...201121899698
Roles of Apicomplexan protein kinases at each life cycle stage.Inhibitors of cellular protein kinases have been reported to inhibit the development of Apicomplexan parasites, suggesting that the functions of protozoan protein kinases are critical for their life cycle. However, the specific roles of these protein kinases cannot be determined using only these inhibitors without molecular analysis, including gene disruption. In this report, we describe the functions of Apicomplexan protein kinases in each parasite life stage and the potential of pre-existing p ...201122209882
Dramatic decrease in malaria transmission after large-scale indoor residual spraying with bendiocarb in Benin, an area of high resistance of Anopheles gambiae to pyrethroids.In 2008, the National Malaria Control Program in Benin implemented a vector control intervention based on indoor residual spraying (IRS). Four districts of high resistance of Anopheles gambiae to pyrethroids were sprayed with bendiocarb. More than 350,000 inhabitants have been protected. Entomologic parameters in the control area were compared with those in intervention sites. The study has shown a drastic decrease in the An. gambiae biting rate in the sprayed areas. Results of an enzyme-linked ...201121976555
Redox-active antiparasitic drugs.Significance: Parasitic diseases affect hundreds of millions of people worldwide and represent major health problems. Treatment is becoming extremely difficult due to the emergence of drug-resistance, the absence of effective vaccines and the spread of insecticide-resistant vectors. Thus, identification of affordable and readily available drugs against resistant parasites is of global demand. Recent Advances: Susceptibility of many parasites to oxidative stress is a well-known phenomenon. There ...201122122517
Screening medicinal plants for the detection of novel antimalarial products applying the inhibition of ß-hematin formation.The identification of novel scaffolds for the development of effective and safe treatments to fight malaria is urgently needed. One of the main opportunities is the discovery of new molecules from natural origin. A simple, robust and cost-effective colorimetric assay based on the inhibition of ß-hematin has been adapted to routinely screen plant extracts with the ultimate goal to identify novel antimalarial ingredients. The development of this assay has included a careful optimization of all cri ...201121872416
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