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A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs.Critical to the development of new drugs for treatment of malaria is the capacity to safely evaluate their activity in human subjects. The approach that has been most commonly used is testing in subjects with natural malaria infection, a methodology that may expose symptomatic subjects to the risk of ineffective treatment. Here we describe the development and pilot testing of a system to undertake experimental infection using blood stage Plasmodium falciparum parasites (BSP). The objectives of t ...201121887214
Timing the origin of human malarias: the lemur puzzle.ABSTRACT:201121992100
review: malaria chemoprophylaxis for travelers to latin america.because of recent declining malaria transmission in latin america, some authorities have recommended against chemoprophylaxis for most travelers to this region. however, the predominant parasite species in latin america, plasmodium vivax, can form hypnozoites sequestered in the liver, causing malaria relapses. additionally, new evidence shows the potential severity of vivax infections, warranting continued consideration of prophylaxis for travel to latin america. individualized travel risk asses ...201122144437
indolone-n-oxide derivatives: in vitro activity against fresh clinical isolates of plasmodium falciparum, stage specificity and in vitro interactions with established antimalarial drugs.indolone-n-oxides are characterized by the presence of a highly reactive pharmacophore, the nitrone moiety (c=n(+)-o(-)), which undergoes oxidation-reduction reactions. the aims of the present study were to: (i) evaluate the in vitro activity of the parent compound, designated as compound 1, against 34 fresh clinical isolates of plasmodium falciparum; (ii) compare the activity of compound 1 with that of chloroquine and dihydroartemisinin to assess the potential for cross-resistance; (iii) invest ...201121862474
furfuran lignans and a flavone from artemisia gorgonum webb and their in vitro activity against plasmodium falciparum.the chemical composition of the aerial parts of the cape verdean endemic shrub artemisia gorgonum webb (asteraceae) was careful investigated, which led to the isolation and identification of six known furfuran lignans: eudesmin (1), magnolin (2), epimagnolin a (3), aschantin (4), kobusin (5), sesamin (6) and a flavone: artemetin (7). compounds 1-7 were evaluated in vitro for their cytotoxicity in a screening panel consisting of various mammalian tumor cell lines, for their antimalarial activity ...201121982788
fluorescence microscope (cyscope) for malaria diagnosis in pregnant women in medani hospital, sudan.accuracy of diagnosis is the core for malaria control. although microscopy is the gold standard in malaria diagnosis, its reliability is largely dependent on user skill. we compared performance of cyscope fluorescence microscope with the giemsa stained light microscopy for the diagnosis of malaria among pregnant women at medani hospital in central sudan. the area is characterized by unstable malaria transmission.201121943212
antibodies to plasmodium falciparum antigens and the risk of clinical malaria in endemic populations.as the research for the development of a malaria vaccine becomes increasingly important, a thorough understanding of the protection afforded by antibodies against parasite antigens is essential. the factors affecting the protective ability of antibodies elicited by highly immunogenic malaria parasite antigens and their interaction have been investigated in a study of ugandan children by greenhouse and colleagues. their interesting finding of the effect of prior exposure on the protection provide ...201122029518
the role of amino acid electron-donor/acceptor atoms in host-cell binding peptides is associated with their 3d structure and hla-binding capacity in sterile malarial immunity induction.plasmodium falciparum malaria continues being one of the parasitic diseases causing the highest worldwide mortality due to the parasite's multiple evasion mechanisms, such as immunological silence. membrane and organelle proteins are used during invasion for interactions mediated by high binding ability peptides (habps); these have amino acids which establish hydrogen bonds between them in some of their critical binding residues. immunisation assays in the aotus model using habps whose critical ...201122197813
Assessing rapid diagnostic tests for malaria. 201121901735
positive selection on the plasmodium falciparum clag2 gene encoding a component of the erythrocyte-binding rhoptry protein complex.a protein complex of high-molecular-mass proteins (pfrhoph) of the human malaria parasite plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. clarification of the level of polymorphism and the evolutionary processes is important both for vaccine design and for a better understanding of the evolution of cell invasion in this parasite. in a previous study on 5 genes encoding rhoph1/clag proteins, positive diversifying selection was detected ...201122028613
the abundance and host-seeking behavior of culicine species (diptera: culicidae) and anopheles sinensis in yongcheng city, people's republic of china.abstract: background: the knowledge of mosquito species diversity and the level of anthropophily exhibited by each species in a region are of great importance to the integrated vector control. culicine species are the primary vectors of japanese encephalitis (je) virus and filariasis in china. anopheles sinensis plays a major role in the maintenance of plasmodium vivax malaria transmission in china. the goal of this study was to compare the abundance and host-seeking behavior of culicine specie ...201122115320
plasmodium knowlesi: an overlooked italian discovery? 201121890752
Distribution pattern of Plasmodium falciparum chloroquine transporter (pfcrt) gene haplotypes in Sri Lanka 1996-2006.Widespread antimalarial resistance has been a barrier to malaria elimination efforts in Sri Lanka. Analysis of genetic markers in historic parasites may uncover trends in the spread of resistance. We examined the frequency of Plasmodium falciparum chloroquine transporter (pfcrt; codons 72-76) haplotypes in Sri Lanka in 1996-1998 and 2004-2006 using a high-resolution melting assay. Among 59 samples from 1996 to 1998, we detected the SVMNT (86%), CVMNK (10%), and CVIET (2%) haplotypes, with a posi ...201122049031
Exploratory analysis of genomic segmentations with Segtools.As genome-wide experiments and annotations become more prevalent, researchers increasingly require tools to help interpret data at this scale. Many functional genomics experiments involve partitioning the genome into labeled segments, such that segments sharing the same label exhibit one or more biochemical or functional traits. For example, a collection of ChlP-seq experiments yields a compendium of peaks, each labeled with one or more associated DNA-binding proteins. Similarly, manually or aut ...201122029426
Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia.ABSTRACT: BACKGROUND: Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis. METHODS: A cross sectional study was conducted in the north-east coast of Tanzania to investigate whether t ...201122206234
In Vitro and In Vivo Activity of Solithromycin (CEM-101) Against Plasmodium Species.With the emergence of Plasmodium falciparum infections exhibiting increased parasite clearance times in response to treatment with artemisinin-based combination therapies, the need for new therapeutic agents is urgent. Solithromycin, a potent new fluoroketolide currently in development, has been shown to be an effective, broad-spectrum antimicrobial agent. Malarial parasites possess an unusual organelle, termed the apicoplast, which carries a cryptic genome of prokaryotic origin that encodes its ...201122083475
Antiplasmodial Alkaloids from the Stem Bark of Strychnos malacoclados.From the stem bark of STRYCHNOS MALACOCLADOS, one new bisindole alkaloid, 3-hydroxylongicaudatine Y ( 1), was isolated along with the known alkaloids vomicine ( 2), bisnordihydrotoxiferine ( 3), divarine ( 4), longicaudatine ( 5), longicaudatine Y ( 6), and longicaudatine F ( 7). All the compounds were tested for their antimalarial activity against the chloroquine-sensitive 3D7 and -resistant W2 strains of PLASMODIUM FALCIPARUM. Longicaudatine was the most active compound with IC (50) values o ...201122193980
antimalarial activity of physalins b, d, f, and g.the antimalarial activities of physalins b, d, f, and g (1-4), isolated from physalis angulata, were investigated. in silico analysis using the similarity ensemble approach (sea) database predicted the antimalarial activity of each of these compounds, which were shown using an in vitro assay against plasmodium falciparum. however, treatment of p. berghei-infected mice with 3 increased parasitemia levels and mortality, whereas treatment with 2 was protective, causing a parasitemia reduction and a ...201121954931
recent clinical and molecular insights into emerging artemisinin resistance in plasmodium falciparum.artemisinin-based combination therapies (acts) have been deployed globally with remarkable success for more than 10 years without having lost their malaria treatment efficacy. however, recent reports from the thai-cambodian border reveal evidence of emerging resistance to artemisinins. the latest published clinical and molecular findings are summarized herein.201122001944
naturally acquired immune responses to plasmodium falciparum sexual stage antigens pfs48/45 and pfs230 in an area of seasonal transmission.acquisition of immunity to plasmodium falciparum sexual stages is a key determinant for reducing human-mosquito transmission by preventing the fertilization and the development of the parasite in the mosquito midgut. naturally acquired immunity against sexual stages may therefore form the basis for the development of transmission-blocking vaccines, but studies conducted to date offer little in the way of consistent findings. here, we describe the acquisition of antigametocyte immune responses in ...201121969000
eritrean and sudanese migrants presenting with malaria in israel.in israel, a malaria-free country, we have noticed lately an increase of hospital admissions with malaria, parallel to the rise in the number of eritrean and sudanese migrants. eritrea and sudan are malaria-endemic countries; plasmodium falciparum accounts for 85-90% and plasmodium vivax accounts for 10-15% of malaria species in these areas. we aimed to describe the features of malaria in this migrant population by conducting a retrospective descriptive study of eritrean and sudanese migrants ad ...201122037052
the in vivo anti-plasmodial activity of haliclonacyclamine a, an alkaloid from the marine sponge, haliclona sp.the compound haliclonacyclamine a was isolated from the haliclona sponge at solomon islands. it acts as a powerful in vitro and in vivo anti-plasmodial agent against the chloroquine-resistant plasmodium falciparum strain fcb1and plasmodium vinckei petteri-infected mice, respectively.201121895455
wolbachia induces reactive oxygen species (ros)-dependent activation of the toll pathway to control dengue virus in the mosquito aedes aegypti.wolbachia are maternally transmitted symbiotic bacteria that can spread within insect populations because of their unique ability to manipulate host reproduction. when introduced to nonnative mosquito hosts, wolbachia induce resistance to a number of human pathogens, including dengue virus (denv), plasmodium, and filarial nematodes, but the molecular mechanism involved is unclear. in this study, we have deciphered how wolbachia infection affects the aedes aegypti host in inducing resistance to d ...201122123956
research challenges and gaps in malaria knowledge in papua new guinea.taking into consideration the relative number of people living in papua new guinea the burden of malaria in this country is among the highest in asia and the pacific region. this article summarizes the research questions and challenges being undertaken by the southwest pacific international center of excellence for malaria research in the context of the epidemiology, transmission and pathogenesis of plasmodium falciparum and p. vivax at the present time and the recent past. it is hoped that the ...201121896268
erythrocyte remodeling in plasmodium berghei infection: the contribution of sep family members.the malaria parasite plasmodium largely modifies the infected erythrocyte through the export of proteins to multiple sites within the host cell. this remodeling is crucial for pathology and translocation of virulence factors to the erythrocyte surface. in this study, we investigated localization and export of small exported proteins/early transcribed membrane proteins (sep/etramps), conserved within plasmodium genus. this protein family is characterized by a predicted signal peptide, a short lys ...201122106924
elevated plasma von willebrand factor and propeptide levels in malawian children with malaria.in spite of the significant mortality associated with plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. we have previously shown evidence of endothelial activation in ghanaian children with malaria, indicated by elevated plasma levels of both von willebrand factor (vwf) and its propeptide. in the current prospective study of children in malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non m ...201122125593
primaquine in vivax malaria: an update and review on management issues.abstract: primaquine was officially licensed as an anti-malarial drug by the fda in 1952. it has remained the only fda licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of plasmodium vivax. this update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquin ...201122152065
The company malaria keeps: how co-infection with Epstein-Barr virus leads to endemic Burkitt lymphoma.Co-infection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) are implicated in the cause of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in equatorial Africa. Although the causal association between EBV and eBL has been established, P. falciparum malaria's role is not as clearly defined. This review focuses on how malaria may disrupt EBV persistence and immunity.201121885920
haemosporidian vector research: marriage of molecular and microscopical approaches is essential.many species of malaria and related haemosporidian parasites (haemosporida) are responsible for diseases in wild and domestic animals. these pathogens are exclusively transmitted by blood-sucking dipteran insects (diptera). traditional vector studies, which are based mainly on experimental infection and subsequent dissection of insects, are time-consuming, so progress in the identification of the vectors has been slow. since the discovery of haemosporidians in wildlife by v. danilewsky in 1884, ...201121901870
Nitric oxide is involved in the upregulation of IFN-? and IL-10 mRNA expression by CD8? T cells during the blood stages of P. chabaudi AS infection in CBA/Ca mice.Nitric oxide (NO) is involved in the clearance of several types of bacteria, viruses and parasites. Although the roles of NO and CD8? T cells in the immune response to malaria have been extensively studied, their actual contributions during the blood stages of malaria infection remain unclear.In this work, we corroborate that serum NO levels are not associated with the in vivo elimination of the blood stages of Plasmodium chabaudi AS. In addition, we show that CD8? T cells exhibit increased apop ...201122110391
harmonine, a defence compound from the harlequin ladybird, inhibits mycobacterial growth and demonstrates multi-stage antimalarial activity.the harlequin ladybird beetle harmonia axyridis has been introduced in many countries as a biological control agent, but has become an invasive species threatening the biodiversity of native ladybirds. its invasive success has been attributed to its vigorous resistance against diverse pathogens. this study demonstrates that harmonine ((17r,9z)-1,17-diaminooctadec-9-ene), which is present in h. axyridis haemolymph, displays broad-spectrum antimicrobial activity that includes human pathogens. anti ...201121937493
functional, immunological and three-dimensional analysis of chemically synthesised sporozoite peptides as components of a fully-effective antimalarial vaccine.our ongoing search for a fully-effective vaccine against the plasmodium falciparum parasite (causing the most lethal form of human malaria) has been focused on identifying and characterising proteins' amino acid sequences (high activity binding peptides or habps) involved in parasite invasion of red blood cells (rbc) by the merozoite and hepatocytes by the sporozoite. many such merozoite habps have been recognised and molecularly and structurally characterised; however, native habps are immunolo ...201122029724
Broad inhibition of Plasmodium falciparum cytoadherence by (+)-epigallocatechin gallate.ABSTRACT: BACKGROUND: The surface antigen PfEMP-1 is a key virulence factor of the human malaria parasite implicated in the cytoadherence of Plasmodium falciparum infected erythrocytes to a range of receptors on host endothelium. Among these host receptors, binding to ICAM-1 is related to cerebral malaria. The majority of the mortality in children with cerebral malaria is seen within 24 h of hospital admission despite the use of effective anti-parasite drugs, therefore, the development of adjun ...201122132804
Conditions of malaria transmission in Dakar from 2007 to 2010.Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010.201122018223
homeostatic proliferation and il-7r alpha expression do not correlate with enhanced t cell proliferation and protection in chronic mouse malaria.while chronic infection has been shown to enhance protection from disease caused by several pathogens, the mechanisms are not known. the gamma-c family of cytokines il-7, il-2, and il-15 are implicated in homeostatic proliferation, which is thought to maintain t cell memory. however in chronic infection, prolonged antigen exposure itself may contribute to lymphocyte survival. we have previously observed that chronic malaria infection enhances protection to re-infection, as well as enhancing b ce ...201122039531
4-thiophenoxy-2-trichloromethyquinazolines display in vitro selective antiplasmodial activity against the human malaria parasite plasmodium falciparum.a series of original quinazolines bearing a 4-thiophenoxy and a 2-trichloromethyl group was synthesized in a convenient and efficient way and was evaluated toward its in vitro antiplasmodial potential. the series revealed global good activity against the k1-multi-resistant plasmodium falciparum strain, especially with hit compound 5 (ic(50)=0.9 μm), in comparison with chloroquine and doxycycline chosen as reference-drugs. both the in vitro cytotoxicity study which was conducted on the human hepg ...201121852132
baseline in vitro activities of the antimalarials pyronaridine and methylene blue against plasmodium falciparum isolates from kenya.we have analyzed the in vitro activities of pyronaridine and methylene blue against 59 plasmodium falciparum isolates from kenya in association with polymorphisms in pfcrt (codon 76), pfmdr1 (codon 86), and pfnhe (full sequence). the median inhibitory concentrations that kill 50% of parasites were 13.5 and 3.3 nm for pyronaridine and methylene blue, respectively. their activities were not associated with polymorphisms in these genes. the drugs' high in vitro activities indicate that they would b ...201122123687
Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax.Plasmodium vivax infection has been gaining attention because of its re-emergence in several parts of the world. Southeastern Turkey is one of the places in which persistent focal malaria caused exclusively by P. vivax parasites occurs. Although control and elimination studies have been underway for many years, no detailed study has been conducted to understand the mechanisms underlying the ineffective control of malaria in this region. Here, for the first time, using serologic markers we try to ...201122140521
Absolute bioavailability of cis-mirincamycin and trans-mirincamycin in healthy rhesus monkeys and ex vivo antimalarial activity against Plasmodium falciparum.The pharmacokinetics, oral bioavailability, and ex vivo antimalarial activity of mirincamycin isomers in a healthy rhesus monkey model were assessed to support lead optimization of novel nonhemolytic drugs for radical cure and causal prophylaxis of malaria. Fourteen male rhesus monkeys were randomized to four groups, which included cis and trans isomers by the oral and intravenous routes, with vehicle-only controls for each dosing route. Concentration-time data were collected for 7 days and were ...201121947400
A new molecular approach for cidal vs static antimalarial determination by quantifying mRNA levels.In order to maximise compliance, the future antimalarial treatment should ideally require just a single-dose administration. This, in turn, demands new fast-acting effective drugs. Currently, methods to measure the in vitro killing rate of antimalarials are based on parasite growth. We have developed and validated a method to determine and classify antimalarial agents based on their cidal or static activity following quantitative Real Time PCR (RT-PCR) analysis. The method described here is a fa ...201122108433
phenotypic screens, chemical genomics, and antimalarial lead discovery. 201121876669
Genomics and Integrated Systems Biology in Plasmodium falciparum: A Path to Malaria Control and Eradication.The first draft of the human malaria parasite's genome was released in 2002. Since then, the malaria scientific community has witnessed a steady embrace of new and powerful functional genomic studies. Over the years, these approaches have slowly revolutionized malaria research and enabled the comprehensive, unbiased investigation of various aspects of the parasite's biology. These genome-wide analyses delivered a refined annotation of the parasite's genome, a better knowledge of its RNA, protein ...201121995286
Sensitive detection and accurate monitoring of Plasmodium vivax parasites on routine complete blood count using automatic blood cell analyzer (DxH800(TM) ).Introduction: Plasmodium vivax malaria is one of the most important infectious diseases plaguing humanity and causes significant mortality and morbidity worldwide. The gold standard of P. vivax malaria diagnosis is the microscopy of blood smears. Although microscopy is a rapid, cost-effective, and readily applicable method, it has many disadvantages, including low sensitivity, specificity, and precision. Therefore, there is a clear need for an effective screening test for P. vivax malaria detec ...201122074115
Antimalaria Effect of the Ethanolic Stem Bark Extracts of Ficus platyphylla Del.The antimalarial effect of the ethanolic stem bark extract of Ficus platyphylla Del was evaluated against Plasmodium berghei infection in mice. Nontreated, experimental control mice died of fulminant parasitemia from day 7 to 9 post-infection but mice treated with the extract at 300?mg/kg showed markedly reduced parasitaemia bouts of 43.50% and a mean survival time of 28 days postinfection. The plant extract prevented a drastic reduction in PCV showing its efficacy in ameliorating anaemic condit ...201122174991
Gametocytogenesis in malaria parasite: commitment, development and regulation.Malaria parasites have evolved a complicated life cycle alternating between two hosts. Gametocytes are produced in the vertebrate hosts and are obligatory for natural transmission of the parasites through mosquito vectors. The mechanism of sexual development in Plasmodium has been the focus of extensive studies. In the postgenomic era, the advent of genome-wide analytical tools and genetic manipulation technology has enabled rapid advancement of our knowledge in this area. Patterns of gene expre ...201122082293
unusual presentation of plasmodium vivax: a neglected human malaria parasite.severe and complicated malaria is usually caused by plasmodium falciparum malaria (pf) but it has been increasingly observed that plasmodium vivax malaria (pv), which was otherwise considered to be benign malaria, with a low case-fatality ratio, can also occasionally result in severe disease as with pf malaria. there is an urgent need to re-examine the clinical spectrum and burden of pv so that adequate control measures can be implemented against this emerging but neglected disease. we report a ...201122205350
seasonal trends in epidemiological and entomological profiles of malaria transmission in north central nigeria.the influence of seasonal changes on epidemiological and entomological indices of malaria transmission in north central nigeria was elucidated in a series of studies carried out between january 2004 and december 2009. the climate in the study area was divided into three seasonal periods namely, rainy (may-october), dry (december-march) and transitional (april and november), during which larval and adult anopheline mosquito collections were carried out and assessed for densities, sporozoite infec ...201121870632
antitumor effect of malaria parasite infection in a murine lewis lung cancer model through induction of innate and adaptive immunity.lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. developing new therapeutic strategies for lung cancer is urgently needed. malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. this study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer.201121931708
malaria in india: the center for the study of complex malaria in india.malaria is a major public health problem in india and one which contributes significantly to the overall malaria burden in southeast asia. the national vector borne disease control program of india reported ∼1.6 million cases and ∼1100 malaria deaths in 2009. some experts argue that this is a serious underestimation and that the actual number of malaria cases per year is likely between 9 and 50 times greater, with an approximate 13-fold underestimation of malaria-related mortality. the difficult ...201122142788
Plasmodium induced by SU6656, an Src family kinase inhibitor, is accompanied by a contractile ring defect.We have shown that SU6656, a potent Src family kinase inhibitor, has the ability to induce multinucleation at a high frequency in diverse cells: rat skin fibroblasts, bone marrow adherent cells, 5F9A mesenchymal stem cell-like clones, 2C5 tracheal epithelial cells and MDCK epithelial cells from dog kidney. To gain insight into the mechanism of multinucleation, we observed the process by time-lapse and confocal microscopy. These multinuclei generally seem to exist independently in one cell withou ...201122034098
calcium storage and function in apicomplexan parasites.calcium is relevant for several vital functions in apicomplexan parasites, including host cell invasion, parasite motility and differentiation. the er (endoplasmic reticulum) and calcium-rich acidocalcisomes have been identified as major calcium stores. other potential calcium-storage organelles include the golgi, the mitochondrion, the apicoplast and the recently described plant-like vacuole in toxoplasma gondii. compared with most eukaryotic systems, apicomplexan parasites contain a reduced nu ...201122023444
[preparation of monoclonal antibody against pfs25 protein and establishment of double antibody sandwich elisa method].to prepare the monoclonal antibody (mab)against pfs25 protein of plasmodium falciparum, and establish the method of sandwich elisa for detecting the pfs25 protein.201122152818
inhibitory effect and mechanism on antiproliferation of khellactone derivatives from herbal suitable for medical or food uses.angelica genus (umbelliferae) has traditionally been used as the medicine and health food considered alleviating several used in the treatment of cancer as well as non-cancerous diseases. angelica purpuraefolia chung is an endemic species and a folk medicine in korea. we have previously reported that two natural khellactone isolated from the rhizomes of a. purpuraefolia has significant antiplasmodial activity against plasmodium falciparum. in the present study, we scientifically evaluated the ef ...201122107989
hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection.hepcidin is one of the regulators of iron metabolism. the expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. recent studies have indicated that serum hepcidin level is also increased in human subjects infected with plasmodium falciparum. the mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. in this study, we determined the expression of hepcidin in livers of mice infected with plasmodium be ...201122084434
Plasmodium vivax lineages: geographical distribution, tandem repeat polymorphism, and phylogenetic relationship.ABSTRACT: BACKGROUND: Multi-drug resistance and severe/complicated cases are the emerging phenotypes of vivax malaria, which may deteriorate current anti-malarial control measures. The emergence of these phenotypes could be associated with either of the two Plasmodium vivax lineages. The two lineages had been categorized as Old World and New World, based on geographical sub-division and genetic and phenotypical markers. This study revisited the lineage hypothesis of P. vivax by typing the distr ...201122182774
Considerations on the use of nucleic acid-based amplification for malaria parasite detection.Nucleic acid amplification provides the most sensitive and accurate method to detect and identify pathogens. This is primarily useful for epidemiological investigations of malaria because the infections, often with two or more Plasmodium species present simultaneously, are frequently associated with microscopically sub-patent parasite levels and cryptic mixed infections. Numerous distinct equally adequate amplification-based protocols have been described, but it is unclear which to select for ep ...201122034851
An exhaustive, non-euclidean, non-parametric data mining tool for unraveling the complexity of biological systems--novel insights into malaria.Complex, high-dimensional data sets pose significant analytical challenges in the post-genomic era. Such data sets are not exclusive to genetic analyses and are also pertinent to epidemiology. There has been considerable effort to develop hypothesis-free data mining and machine learning methodologies. However, current methodologies lack exhaustivity and general applicability. Here we use a novel non-parametric, non-euclidean data mining tool, HyperCube®, to explore exhaustively a complex epidemi ...201121931645
Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dys ...201122157630
Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites.Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human geno ...201121867552
Malaria vaccine results face scrutiny. 201122031413
histidine affinity tags affect msp1(42) structural stability and immunodominance in mice.inclusion of affinity tags has greatly facilitated process development for protein antigens, primarily for their recovery from complex mixtures. although generally viewed as supportive of product development, affinity tags may have unintended consequences on protein solubility, susceptibility to aggregation, and immunogenicity. merozoite surface protein 1 (msp1), an erythrocytic stage protein of plasmodium falciparum and a candidate malaria vaccine, was used to evaluate the impact of a metal ion ...201122076863
nematode-induced interference with the anti-plasmodium cd8(+) t-cell response can be overcome by optimizing antigen administration.malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. here we show that strongyloides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against plasmodium berghei. an ongoing infection with litomosoides sigmodontis, a tissue-dwelling filaria that induces chr ...201122161305
similar efficacy and safety of artemether-lumefantrine (coartem(r)) in african infants and children with uncomplicated falciparum malaria across different body weight ranges.abstract: background: artemisinin-based combination therapy, including artemether-lumefantrine (al), is currently recommended for the treatment of uncomplicated plasmodium falciparum malaria. the objectives of the current analysis were to compare the efficacy and safety of al across different body weight ranges in african children, and to examine the age and body weight relationship in this population. methods: efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, m ...201122176931
molecular markers of anti-malarial drug resistance in lahj governorate, yemen: baseline data and implications.this is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (cq) against falciparum malaria in an area of unstable malaria in lahj governorate, yemen. the study was aimed at assessment of therapeutic response to cq and elucidation of baseline information on molecular markers for plasmodium falciparum resistance against cq and sulphadoxine/pyrimethamine (sp).201121854642
diversity and distribution of avian haematozoan parasites in the western indian ocean region: a molecular survey.summarythe genetic diversity of haematozoan parasites in island avifauna has only recently begun to be explored, despite the potential insight that these data can provide into the history of association between hosts and parasites and the possible threat posed to island endemics. we used mitochondrial dna sequencing to characterize the diversity of 2 genera of vector-mediated parasites (plasmodium and haemoproteus) in avian blood samples from the western indian ocean region and explored their re ...201122075855
Helichrysum gymnocephalum essential oil: chemical composition and cytotoxic, antimalarial and antioxidant activities, attribution of the activity origin by correlations.Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%), ?-curcumene (5.6%), a-amorphene (5.1%) and bicyclogermacrene (5%) were the main components. Our results confirmed the important chemical variability of H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human breast cancer cells MCF-7), ...201121959299
molecular monitoring of resistant dhfr and dhps allelic haplotypes in morogoro and mvomero districts in south eastern tanzania.resistance to the antimalarial drug sulfadoxine-pyrimethamine (sp) emerged in plasmodium falciparum from asia in the 1960s and subsequently spread to africa. in tanzania, sp use as a national policy began in 1983 as a second line to chloroquine (cq) for the treatment of uncomplicated malaria, until august 2001 when it was approved to replace cq as a national first line.201121857842
disruption of a mitochondrial protease machinery in plasmodium falciparum is an intrinsic signal for parasite cell death.the atp-dependent clpqy protease system in plasmodium falciparum is a prokaryotic machinery in the parasite. in the present study, we have identified the complete clpqy system in p. falciparum and elucidated its functional importance in survival and growth of asexual stage parasites. we characterized the interaction of p. falciparum clpq protease (pfclpq) and pfclpy atpase components, and showed that a short stretch of residues at the c terminus of pfclpy has an important role in this interactio ...201122113196
searching for artemisinin production improvement in plants and microorganisms.the endoperoxide sesquiterpene lactone artemisinin which is isolated from the plant artemisia annua, and its semi-synthetic derivatives, are potent, novel, antimalarial drugs. they are effective against multidrug-resistant plasmodium strains and have become essential components of the so-called artemisinin-based combination therapy, that is recommended by the world health organization as the treatment of choice for malaria tropica. moreover, artemisinin and its derivatives show additional anti-p ...201121902625
il-27 promotes il-10 production by effector th1 cd4+ t cells: a critical mechanism for protection from severe immunopathology during malaria infection.infection with the malaria parasite, plasmodium, is characterized by excessive inflammation. the establishment of a precise balance between the pro- and anti-inflammatory responses is critical to guarantee control of the parasite and survival of the host. il-10, a key regulatory cytokine produced by many cells of the immune system, has been shown to protect mice against pathology during acute plasmodium0 chabaudi chabaudi as model of malaria. however, the critical cellular source of il-10 is sti ...201122205023
methods to collect anopheles mosquitoes and evaluate malaria transmission: a comparative study in two villages in senegal.various methods have been studied as replacement of human landing catches (hlc) for mosquito sampling in entomological studies on malaria transmission. conflicting results have been obtained in comparing relative efficiency of alternative methods, according to the area, the species present and their density. the aim of this study was to compare the number and characteristics of mosquitoes sampled in two areas of senegal by three different methods: hlc, light traps adjacent to an occupied bed net ...201121929747
reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from south-east asia.decreased in vitro susceptibility to dihydroartemisinin (21.2 nm) and artesunate (16.3 nm) associated with decreased susceptibility or resistance to quinine (1131 nm), mefloquine (166 nm), lumefantrine (114 nm), pyronaridine (70.5 nm) and piperaquine (91.1 nm) is reported in a patient returning from south-east asia after trekking along the mekong from the south of laos to the north of thailand. decreased in vitro susceptibility to artemisinin derivatives did not appear to be mediated by the numb ...201121923936
the next opportunity in anti-malaria drug discovery: the liver stage. 201121966266
δe1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against plasmodium falciparum.background: the merozoite surface protein 1 (msp-1) of plasmodium falciparum, the causative agent of malaria tropica, is considered a promising vaccine candidate. though its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described herein. methods: codon-optimized msp-1 was used to construct a set of first generation (δe1 ad) and high-capacity adenovirus (hc-ad) vectors and cellular and humoral immune responses induced by the ve ...201122095915
Species-Specific Features of DARC, the Primate Receptor for Plasmodium vivax and Plasmodium knowlesi.The DARC (Duffy antigen/receptor for chemokines) gene, also called Duffy or FY, encodes a membrane-bound chemokine receptor. Two malaria parasites, Plasmodium vivax and Plasmodium knowlesi, use DARC to trigger internalization into red blood cells. Although much has been reported on the evolution of DARC null alleles, little is known about the evolution of the coding portion of this gene or the role that protein sequence divergence in this receptor may play in disease susceptibility or zoonosis. ...201121878684
study and evaluation of wondfo rapid diagnostic kit based on nano-gold immunochromatography assay for diagnosis of plasmodium falciparum.malaria has been recognized as a human disease for thousands of years and remains one of the most common diseases affecting humans worldwide. therefore, a method for rapidly detecting plasmodium falciparum is necessary and useful. we have developed wondfo rapid diagnostic kit based on nano-gold immunochromatography assay for the detection of p. falciparum in patient specimen. in the present study, we demonstrated the sensitivity and specificity of the rapid diagnostic kit in which nano-gold labe ...201121922236
changing transmission pattern of plasmodium vivax malaria in the republic of korea: relationship with climate change.plasmodium vivax malaria has occurred annually in the republic of korea (rok) since its re-emergence in 1993. p. vivax malaria in rok has been strongly influenced by infected mosquitoes originating from the democratic people's republic of korea. korean p. vivax malaria has shown typical characteristics of unstable malaria transmitted only during the summer season, and displays short and long incubation periods. the changing pattern of the transmission period can be predicted by analyzing the sea ...201122125762
protein-based signatures of functional evolution in plasmodium falciparum.it has been known for over a decade that plasmodium falciparum proteins are enriched in non-globular domains of unknown function. the potential for these regions of protein sequence to undergo high levels of genetic drift provides a fundamental challenge to attempts to identify the molecular basis of adaptive change in malaria parasites.201121917172
blood stage merozoite surface protein conjugated to nanoparticles induce potent parasite inhibitory antibodies.in this proof-of-concept study we report the use of <15 nm, water soluble, inorganic nanoparticles as a vaccine delivery system for a blood stage malaria vaccine. the recombinant malarial antigen, merozoite surface protein 1 (rmsp1) of plasmodium falciparum served as the model vaccine. the rmsp1 was covalently conjugated to polymer-coated quantum dot cdse/zns nanoparticles (qds) via surface carboxyl groups, forming rmsp1-qds. anti-msp1 antibody responses induced by rmsp1-qds were found to have 2 ...201121963870
recent advances in the study of avian malaria: an overview with an emphasis on the distribution of plasmodium spp in brazil.avian malaria parasites (plasmodium) have a worldwide distribution except for antarctica. they are transmitted exclusively by mosquito vectors (diptera: culicidae) and are of particular interest to health care research due to their phylogenetic relationship with human plasmodia and their ability to cause avian malaria, which is frequently lethal in non-adapted avian hosts. however, different features of avian plasmodium spp, including their taxonomy and aspects of their life-history traits, need ...201121881752
Presence and seasonal prevalence of Plasmodium spp. in a rare endemic New Zealand passerine (tieke or Saddleback, Philesturnus carunculatus).The conservation and management of Saddlebacks (Philesturnus carunculatus) and other New Zealand birds, currently relies on the translocation of individuals to predator-free sites. Avian malaria has been identified as one of the diseases to be tested for prior to translocations in New Zealand, with the aim of translocating disease-free individuals. We describe avian malaria lineages and their seasonal prevalence in 2007-2008 in Saddlebacks from Mokoia Island, a source of birds for translocations ...201122102656
Trial shows vaccine halves malaria episodes in children in Africa. 201122016456
Effect of a(+)-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania.It is controversial to what degree a(+)-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium.201121939508
Sterostreins A-E, new terpenoids from cultures of the Basidiomycete Stereum ostrea BCC 22955.Sterostreins A-E (1, 2, 3a/3b, 4, and 5), five novel terpenoids, were isolated from cultures of the mushroom fungus Stereum ostrea BCC 22955. Sterostrein A (1) exhibited antimalarial activity (IC(50) 2.3 µg/mL) and cytotoxicity (IC(50) 5.3-38 µg/mL).201121848293
Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharide moiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice.Methylotrophic yeast (Pichia pastoris) secreted cholera toxin B subunit (CTB) predominantly as a biologically active pentamer (PpCTB) with identical ganglioside binding affinity profiles to that of choleragenoid. Unlike choleragenoid, however, the PpCTB did not induce a footpad edema response in mice. Of the two potential glycosylation sites (NIT(4-6) and NKT(90-92)) for this protein, a N-linked oligosaccharide was identified at Asn4. The oligosaccharide, presumed to extend from the lateral circ ...201122119928
asymptomatic carriage of malaria parasites in blood donors in yaoundébackground: malaria can be transmitted through blood transfusion, but there is paucity of data concerning transfusion-transmitted malaria in cameroun. objective: to determine prevalence of malaria infection and association with epidemiological and clinical data obtained from donors' responses. methods: microscopic examination of stained thick and thin blood smears for the detection, quantification and specification of plasmodium sp was performed on 493 blood donors in two main hospitals in yaoun ...201122141368
expressed sequence tag analysis of the erythrocytic stage of plasmodium berghei.rodent malaria parasites, such as plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. exploiting the available genetic sequence information, we constructed a cdna library from the erythrocytic stages of p. berghei and analyzed the expressed sequence tag (est). a total of 10,040 ests were generated and assembled into 2,462 clusters. these est clusters were compare ...201122072821
17-o-acetyl,10-hydroxycorynantheol, a selective antiplasmodial alkaloid isolated from strychnos usambarensis leaves.in the course of our investigations on strychnos usambarensis leaves in order to isolate isostrychnopentamine, the main alkaloid responsible for the antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been isolated: 17-o-acetyl,10-hydroxycorynantheol 1. its structure was determined by means of spectroscopic and spectrometric methods such as uv, ir, cd, nmr, and esi-ms. 17-o-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric indole alkaloids known to date ...201121870325
sequence similarity between the erythrocyte binding domain of the plasmodium vivax duffy binding protein and the v3 loop of hiv-1 strain mn reveals a functional heparin binding motif involved in binding to the duffy antigen receptor for chemokines.abstract:201122122911
antimalarial β-carboline and indolactam alkaloids from marinactinospora thermotolerans, a deep sea isolate.four new β-carboline alkaloids, designated marinacarbolines a-d (1-4), two new indolactam alkaloids, 13-n-demethyl-methylpendolmycin (5) and methylpendolmycin-14-o-α-glucoside (6), and the three known compounds 1-acetyl-β-carboline (7), methylpendolmycin (8), and pendolmycin (9) were obtained from the fermentation broth of marinactinospora thermotolerans scsio 00652, a new actinomycete belonging to the family nocardiopsaceae. their structures were elucidated by extensive ms and 1d and 2d nmr spe ...201121977916
effect of transmission reduction by insecticide-treated bednets (itns) on antimalarial drug resistance in western kenya.despite the clear public health benefit of insecticide-treated bednets (itns), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. in the present study, the effect of sustained transmission reduction by itns on the prevalence of plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (sp) and chloroquine (cq) in children under the age of five years was investigated duri ...201122096496
source of the human malaria parasite plasmodium falciparum. 201121903922
rectal artesunates, their utilization, and parental perception in the management of malaria in children from abeokuta, southwestern nigeria.abstract utilization, efficacy, perception, and acceptability of rectal artesunates for treatment of malaria were assessed in 264 children below 5 years attending two tertiary health facilities in abeokuta, nigeria. the children systematically selected were 136 from state hospital ijaye and 128 from federal medical centre (fmc), idi-aba. body weights and vital statistics of the children were measured; and blood samples were collected before and 24 h after administration of the rectal artesunat ...201122022814
cost-effectiveness of the introduction of a pre-erythrocytic malaria vaccine into the expanded program on immunization in sub-saharan africa: analysis of uncertainties using a stochastic individual-based simulation model of plasmodium falciparum malaria.to evaluate the cost-effectiveness of introducing the rts,s malaria vaccine into the expanded programme on immunization (epi) in sub-saharan africa (ssa), the contributions of different sources of uncertainty, and the associated expected value of perfect information (evpi).201122152171
sequestration and microvascular congestion are associated with coma in human cerebral malaria.the pathogenesis of coma in severe plasmodium falciparum malaria remains poorly understood. obstruction of the brain microvasculature because of sequestration of parasitized red blood cells (prbcs) represents one mechanism that could contribute to coma in cerebral malaria. quantitative postmortem microscopy of brain sections from vietnamese adults dying of malaria confirmed that sequestration in the cerebral microvasculature was significantly higher in patients with cerebral malaria (cm; n = 21) ...201122207648
bayesian geostatistical modelling of malaria and lymphatic filariasis infections in uganda: predictors of risk and geographical patterns of co-endemicity.in uganda, malaria and lymphatic filariasis (causative agent wuchereria bancrofti) are transmitted by the same vector species of anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. in a comprehensive nationwide survey in 2000-2003 the geographical distribution of w. bancrofti was assessed by screening school-aged children for circulating filarial antigens (cfa). concurrently, blood smears were examined for malaria parasites. in ...201121989409
discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities.a series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of plasmodium falciparum in vitro. all analogues showed growth inhibitory activity against p. falciparum at less than 3 μm, with the majority having effective ic(50) values in the 100-650 nm range. analogues arrested parasitic growth within 24 h of exposure due to a block in nuclear division and therefore asexual deve ...201121882831
control of plasmodium falciparum erythrocytic cycle: γδ t cells target the red blood cell-invasive merozoites.the control of plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, because it prevents pathogenesis and progression toward severe disease. p falciparum blood-stage parasite cultures are inhibited by human vγ9vδ2 γδ t cells, but the underlying mechanism remains poorly understood. here, we show that both intraerythrocytic parasites and the extracellular red blood cell-invasive merozoites specifically activate vγ9vδ2 t cells in a γδ t cell receptor-depen ...201122045985
genetic analysis of the merozoite surface protein-1 block 2 allelic types in plasmodium falciparum clinical isolates from lao pdr.abstract: background: msp-1 is one of the potential malarial vaccine candidate antigens. however, extensive genetic polymorphism of this antigen in the field isolates of plasmodium falciparum represents a major hindrance for the development of an effective vaccine. therefore, this study aimed to establish the prevalence and genetic polymorphisms of k1, mad20 and ro33 allelic types of msp-1 block 2 among p. falciparum clinical isolates from lao pdr. methods: plasmodium falciparum isolates were c ...201122177111
circulating soluble endoglin levels in pregnant women in cameroon and malawi--associations with placental malaria and fetal growth restriction.placental infections with plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (lbw). the mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. soluble endoglin (seng), a soluble receptor of transforming growth factor (tgf)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune ...201121966395
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