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enhanced sensitivity for detection of plasmodium falciparum gametocytes by magnetic nanoparticles combined with enzyme substrate system.the highly sensitive and specific detection of pfg377 gene of plasmodium falciparum gametocyte using magnetic nanoparticles pcr enzyme-linked gene assay (melga) was successfully developed. the melga included amplification of the pfg377 gene by polymerase chain reaction (pcr) using magnetic nanoparticles (mnps)-conjugated forward primer and biotinylated reverse primer, followed by post-analytical process using horseradish peroxidase (hrp)-conjugated streptavidin (sa). the complexes of melga produ ...201728107985
the role of heme-oxygenase-1 in pathogenesis of cerebral malaria in the co-culture model of human brain microvascular endothelial cell and itg plasmodium falciparum-infected red blood cells.to investigate the role of human host heme-oxygenase-1 (ho-1) in pathogenesis of cerebral malaria in the in vitro model.201728107860
esterase mutation is a mechanism of resistance to antimalarial compounds.pepstatin is a potent peptidyl inhibitor of various malarial aspartic proteases, and also has parasiticidal activity. activity of pepstatin against cultured plasmodium falciparum is highly variable depending on the commercial source. here we identify a minor contaminant (pepstatin butyl ester) as the active anti-parasitic principle. we synthesize a series of derivatives and characterize an analogue (pepstatin hexyl ester) with low nanomolar activity. by selecting resistant parasite mutants, we f ...201728106035
sugar nucleotide quantification by liquid chromatography tandem mass spectrometry reveals a distinct profile in plasmodium falciparum sexual stage parasites.the obligate intracellular lifestyle of plasmodium falciparum and the difficulties in obtaining sufficient amounts of biological material have hampered the study of specific metabolic pathways in the malaria parasite. thus, for example, the pools of sugar nucleotides required to fuel glycosylation reactions have never been studied in-depth in well-synchronized asexual parasites or in other stages of its life cycle. these metabolites are of critical importance, especially considering the renewed ...201728104756
lack of association of cd55 receptor genetic variants and severe malaria in ghanaian children.in a recent report, the cellular receptor cd55 was identified as a molecule essential for the invasion of human erythrocytes by plasmodium falciparum, the causal agent of the most severe form of malaria. as this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (sm) susceptibility. we performed high-resolution variant discovery of rare and common genetic variants in the human cd55 gene ...201728104671
spatio-temporal analysis of the genetic diversity and complexity of plasmodium falciparum infections in kedougou, southeastern senegal.genetic analyses of the malaria parasite population and its temporal and spatial dynamics could provide an assessment of the effectiveness of disease control strategies. the genetic diversity of plasmodium falciparum has been poorly documented in senegal, and limited data are available from the kedougou region. this study examines the spatial and temporal variation of the genetic diversity and complexity of p. falciparum infections in acute febrile patients in kedougou, southeastern senegal. a t ...201728103905
effects of plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a doppler ultrasound study from papua new guinea.doppler velocimetry studies of umbilical artery (ua) and middle cerebral artery (mca) flow help to determine the presence and severity of fetal growth restriction. increased ua resistance and reduced mca pulsatility may indicate increased placental resistance and intrafetal blood flow redistribution. malaria causes low birth weight and fetal growth restriction, but few studies have assessed its effects on uteroplacental and fetoplacental blood flow.201728103875
pathogenicity determinants of the human malaria parasite plasmodium falciparum have ancient origins.plasmodium falciparum, the most deadly of the human malaria parasites, is a member of the laverania subgenus that also infects african great apes. the virulence of p. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion traits is poorly understood. to investigate the evolutionary history of the p. falciparum cytoadhesion pathogenicity determinant, we studied adhesion domains from the chimpanzee malaria parasite p. reich ...201728101534
interferon-γ responses to plasmodium falciparum vaccine candidate antigens decrease in the absence of malaria transmission.malaria elimination campaigns are planned or active in many countries. the effects of malaria elimination on immune responses such as antigen-specific ifn- γ responses are not well characterized.201728097063
one-step design of a stable variant of the malaria invasion protein rh5 for use as a vaccine immunogen.many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. for instance, plasmodium falciparum reticulocyte-binding protein homolog 5 (pfrh5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. however, functional rh5 is only expressible in eukaryotic system ...201728096331
insecticide-treated net effectiveness at preventing plasmodium falciparum infection varies by age and season.after increasing coverage of malaria interventions, malaria prevalence remains high in malawi. previous studies focus on the impact of malaria interventions among children under 5 years old. however, in malawi, the prevalence of infection is highest in school-aged children (sac), ages 5 to 15 years. this study examined the interaction between age group and insecticide-treated net (itn) use for preventing individual and community-level infection in malawi.201728095916
providing lipid-based nutrient supplement during pregnancy does not reduce the risk of maternal p falciparum parasitaemia and reproductive tract infections: a randomised controlled trial.maternal infections are associated with maternal and foetal adverse outcomes. nutrient supplementation during pregnancy may reduce the occurrence of infections by improving maternal immunity. we aimed to investigate the impact of small-quantity lipid-based nutrient supplement (sq-lns) on the occurrence of plasmodium falciparum parasitaemia during pregnancy and trichomoniasis, vaginal candidiasis and urinary tract infection (uti) after delivery.201728095801
glycosides as possible lead antimalarial in new drug discovery: future perspectives.malaria remains one of the major public health problems worldwide and is responsible for a large number of morbidity and mortality. especially, in the third world countries, it is still alarming. the development of drug-resistant to plasmodium falciparum strains has further degraded the overall situation. however, a limited number of effective drugs available emphasizes how essential it is to establish new anti-malarial compounds. new antimalarial agents with distinctive structures and mechanism ...201728093995
a disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria.intra-erythrocytic growth of malaria parasite is known to induce redox stress. in addition to haem degradation which generates reactive oxygen species (ros), the parasite is also thought to efflux redox active homocysteine. to understand the basis underlying accumulation of homocysteine, we have examined the transsulphuration (ts) pathway in the parasite, which is known to convert homocysteine to cysteine in higher eukaryotes. our bioinformatic analysis revealed absence of key enzymes in the bio ...201728091526
griseofulvin impairs intraerythrocytic growth of plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study.griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome p450-mediated production of n-methyl protoporphyrin ix (n-mpp). n-mpp is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage plasmodium falciparum. novel drugs against plasmodium are needed to achieve malaria elimination. thus, we investigated whether griseofulvin shows anti-plasmodial ...201728176804
[rapid diagnostic test for malaria].the rapid diagnostic tests (rdts) whose main interest lies in their implementation without special equipment by unskilled personnel have grown significantly over the past fifteen years to diagnose malaria. they rely on the detection of specific plasmodium proteins, pfhrp2, pldh and aldolase. if the detection of pfhrp2 has very good sensitivity for the diagnosis of plasmodium falciparum malaria, the detection of pldh or aldolase is less efficient for other species, leaving its place to the refere ...201728176239
pre-travel malaria chemoprophylaxis counselling in a public travel medicine clinic in são paulo, brazil.malaria is one of the most prevalent parasitic diseases in the world and represents a threat to travellers visiting endemic areas. chemoprophylaxis is the prevention measure used in travel medicine, avoiding clinical manifestations and protecting against the development of severe disease and death.201728173862
therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated plasmodium falciparum malaria -associated anaemia in nigerian children during seven years of adoption as first-line treatments.artemisinin-based combination treatments (acts) are the first-line treatments of uncomplicated plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children.201728173853
coinfection with schistosoma haematobium and plasmodium falciparum and anaemia severity among pregnant women in munyenge, mount cameroon area: a cross-sectional study.background. malaria and urogenital schistosomiasis are coendemic in mount cameroon area. this study investigated the prevalence of s. haematobium, p. falciparum, and coinfections and their effect on anaemia in pregnancy. methods. pregnant women reporting for antenatal care (anc) clinic visit in munyenge were enrolled. s. haematobium and p. falciparum infections were determined by urine filtration and microscopy, respectively. haemoglobin (hb) levels were measured using haemoglobinometer. of 250 ...201728168042
hidden reservoir of resistant parasites: the missing link in the elimination of falciparum malaria.to successfully eliminate malaria, an integrated system that includes a number of approaches and interventions-aimed at overcoming the threat of antimalarial drug resistance-is required. significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. to consolidate these gains, attention should be paid to the missing links in the elimination of malaria. one of these gaps is the residual reservoir of ...201728166813
an epidemiological study to assess plasmodium falciparum parasite prevalence and malaria control measures in burkina faso and senegal.malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-saharan african countries.201728166794
antibody-independent mechanisms regulate the establishment of chronic plasmodium infection.malaria is caused by parasites of the genus plasmodium. all human-infecting plasmodium species can establish long-lasting chronic infections(1-5), creating an infectious reservoir to sustain transmission(1,6). it is widely accepted that the maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation(7). however, genes involved in this process have been identified in only two of five human-infecting species: plasmodium falciparum and plasmodium knowlesi. furtherm ...201728165471
evolution of the merozoite surface protein 7 (msp7) family in plasmodium vivax and p. falciparum: a comparative approach.malaria parasites (genus plasmodium) are a diverse group found in many species of vertebrate hosts. these parasites invade red blood cells in a complex process comprising several proteins, many encoded by multigene families, one of which is merozoite surface protein 7 (msp7). in the case of plasmodium vivax, the most geographically widespread human-infecting species, differences in the number of paralogs within multigene families have been previously explained, at least in part, as potential ada ...201728163236
the spread of artemisinin-resistant plasmodium falciparum in the greater mekong subregion: a molecular epidemiology observational study.evidence suggests that the pfkelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the greater mekong subregion, which has motivated a regional malaria elimination agenda. we aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the greater mekong subregion.201728161569
evidence of a hard selective sweep for artemisinin resistant plasmodium falciparum. 201728161568
high plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of mali.the effects of persistent plasmodium falciparum (pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. a longitudinal cohort study was conducted in a seasonal and high-transmission area of mali, in which 500 subjects aged 1-65 years were followed for 1 year. blood samples were collected every 2 weeks, and incident malaria cases ...201728158202
accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid c-terminal 'c-tag'.development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept phase i/ii clinical trials. in these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. these chal ...201728153778
anti-malarial synergy of secondary metabolites from morinda lucida benth.the roots, stem and leaves of morinda lucida are used in some african countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth.201728153468
efficacy of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for treatment of uncomplicated plasmodium falciparum malaria in angola, 2015.recent anti-malarial resistance monitoring in angola has shown efficacy of artemether-lumefantrine (al) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. in addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in lunda sul province in 2013.201728153004
efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in somalia: evidence for updating the malaria treatment policy.to determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (as + sp) and artemether + lumefantrine (al), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy.201728151566
a characterization of the antimalarial activity of the bark of cylicodiscus gabunensis harms.a decoction of the bark of cylicodiscus gabunensis harms is used as a traditional medicine in the treatment of malaria in nigeria. this study aims to validate the antimalarial potency of this decoction in vitro against plasmodium falciparum and define potential bioactive constituents within the c. gabunensis bark.201728089716
antibody profiles to wheat germ cell-free system synthesized plasmodium falciparum proteins correlate with protection from symptomatic malaria in uganda.the key targets of protective antibodies against plasmodium falciparum remain largely unknown. in this study, we determined immunoreactivity to 1827 recombinant proteins derived from 1565 genes representing ∼30% of the entire p. falciparum genome, for identification of novel malaria vaccine candidates. the recombinant proteins were expressed by wheat germ cell-free system, a platform that can synthesize quality plasmodial proteins that elicit biologically active antibodies in animals. sera were ...201728089547
direct detection of falciparum and non-falciparum malaria dna from a drop of blood with high sensitivity by the dried-lamp system.because of the low sensitivity of conventional rapid diagnostic tests (rdts) for malaria infections, the actual prevalence of the diseases, especially those caused by non-plasmodium falciparum (non-pf) species, in asymptomatic populations remain less defined in countries lacking in well-equipped facilities for accurate diagnoses. our direct blood dry lamp system (czc-lamp) was applied to the diagnosis of malaria as simple, rapid and highly sensitive method as an alternative for conventional rdts ...201728086864
detection of plasmodium knowlesi, plasmodium falciparum and plasmodium vivax using loop-mediated isothermal amplification (lamp) in a co-endemic area in malaysia.plasmodium knowlesi is the most common cause of malaria in malaysia. however, microscopic diagnosis is inaccurate and rapid diagnostic tests (rdts) are insufficiently sensitive. pcr is sensitive and specific but not feasible at a district level. loop-mediated isothermal amplification (lamp) shows potential with only basic requirements. a commercially available lamp assay, the eiken loopamp™ malaria pan detection kit, is sensitive for plasmodium falciparum and plasmodium vivax, but has not previo ...201728086789
profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of plasmodium falciparum related to resistance to different anti-malarial drugs in the bata district (equatorial guinea).the emergence of drug resistance in plasmodium falciparum has been a major contributor to the global burden of malaria. drug resistance complicates treatment, and it is one of the most important problems in malaria control. this study assessed the level of mutations in p. falciparum genes, pfdhfr, pfdhps, pfmdr1, and pfcrt, related to resistance to different anti-malarial drugs, in the continental region of equatorial guinea, after 8 years of implementing artesunate combination therapies as the ...201728086777
rapid decline in the susceptibility of plasmodium falciparum to dihydroartemisinin-piperaquine in the south of vietnam.artemisinin resistant plasmodium falciparum has emerged in the countries of the greater mekong sub-region posing a serious threat to global malaria elimination efforts. the relationship of artemisinin resistance to treatment failure has been unclear.201728086775
congenital plasmodium falciparum malaria in washington, dc.congenital malaria is rare in the united states, but is an important diagnosis to consider when evaluating febrile infants. herein, we describe a case of congenital plasmodium falciparum malaria in a 2-week-old infant born in the united states to a mother who had emigrated from nigeria 3 months before delivery.201728077745
theoretical implications of a pre-erythrocytic plasmodium vivax vaccine for preventing relapses.preventing malaria infection through vaccination requires preventing every sporozoite inoculated by mosquito bite: a major challenge for plasmodium falciparum. plasmodium vivax sporozoites consist of tachysporozoites causing primary infection and bradysporozoites leading to relapses. we hypothesise that a candidate p. vivax vaccine with low efficacy against primary infection may substantially reduce transmission by preventing relapses.201728077251
population pharmacokinetic properties of piperaquine in falciparum malaria: an individual participant data meta-analysis.artemisinin-based combination therapies (acts) are the mainstay of the current treatment of uncomplicated plasmodium falciparum malaria, but act resistance is spreading across southeast asia. dihydroartemisinin-piperaquine is one of the five acts currently recommended by the world health organization. previous studies suggest that young children (<5 y) with malaria are under-dosed. this study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for ...201728072872
higher complexity of infection and genetic diversity of plasmodium vivax than plasmodium falciparum across all malaria transmission zones of papua new guinea.plasmodium falciparum and plasmodium vivax have varying transmission dynamics that are informed by molecular epidemiology. this study aimed to determine the complexity of infection and genetic diversity of p. vivax and p. falciparum throughout papua new guinea (png) to evaluate transmission dynamics across the country. in 2008-2009, a nationwide malaria indicator survey collected 8,936 samples from all 16 endemic provinces of png. of these, 892 positive p. vivax samples were genotyped at pvms16 ...201728070005
molecular epidemiology of plasmodium falciparum kelch13 mutations in senegal determined by using targeted amplicon deep sequencing.the emergence of plasmodium falciparum resistance to artemisinin in southeast asia threatens malaria control and elimination activities worldwide. multiple polymorphisms in the p. falciparum kelch gene found in chromosome 13 (pfk13) have been associated with artemisinin resistance. surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. in this context, p. falciparum infections from an observational ...201728069653
effectiveness of a serological tool to predict malaria transmission intensity in an elimination setting.sri lanka achieved the who certificate as a malaria free country in september 2016, thus monitoring of malaria transmission using sensitive and effective tools is an important need. use of age-specific antibody prevalence as a serological tool to predict transmission intensity is proven to be a cost effective and reliable method under elimination settings. this paper discusses the correlation of four anti-malarial antibodies against vivax and falciparum malaria with the declining transmission in ...201728068925
characterisation of the opposing effects of g6pd deficiency on cerebral malaria and severe malarial anaemia.glucose-6-phosphate dehydrogenase (g6pd) deficiency is believed to confer protection against plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as g6pd deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of p. falciparum infection. here we report an analysis of multiple allelic forms of g6pd deficiency in a large multi-centre case-control study of s ...201728067620
the role of chromatin structure in gene regulation of the human malaria parasite.the human malaria parasite, plasmodium falciparum, depends on a coordinated regulation of gene expression for development and propagation within the human host. recent developments suggest that gene regulation in the parasite is largely controlled by epigenetic mechanisms. here, we discuss recent advancements contributing to our understanding of the mechanisms controlling gene regulation in the parasite, including nucleosome landscape, histone modifications, and nuclear architecture. in addition ...201728065669
octopus: a platform for the virtual high-throughput screening of a pool of compounds against a set of molecular targets.octopus is an automated workflow management tool that is scalable for virtual high-throughput screening (vhts). it integrates mopac2016, mgltools, pymol, and autodock vina. in contrast to other platforms, octopus can perform docking simulations of an unlimited number of compounds into a set of molecular targets. after generating the ligands in a drawing package in the protein data bank (pdb) format, octopus can carry out geometry refinement using the semi-empirical method pm7 implemented in mopa ...201728064377
determination of glutathione redox potential and ph value in subcellular compartments of malaria parasites.the malaria parasite plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the anopheles vector and its human host. in order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor rogfp2 coupled to human glutaredoxin 1 (rogfp2-hgrx1) as well as the ratiometric ph sensor phluorin to the apicoplast and the mitochondrion of p. falciparum. using ...201728062360
community perceptions of targeted anti-malarial mass drug administrations in two provinces in vietnam: a quantitative survey.as part of a targeted malaria elimination project, mass drug administrations (mdas) were conducted in vietnam. the impact of mdas on malaria transmission depends largely on the efficacy of the anti-malarial drug regimen, the malaria epidemiology in the site and the population coverage. to explore why some people participate in mdas and others do not, a quantitative survey of the villagers' perceptions was undertaken in vietnam.201728061908
malaria epidemiology in central myanmar: identification of a multi-species asymptomatic reservoir of infection.the spread of artemisinin-resistant plasmodium falciparum is a global health concern. myanmar stands at the frontier of artemisinin-resistant p. falciparum. myanmar also has the highest reported malaria burden in southeast asia; it is integral in the world health organization's plan to eliminate malaria in southeast asia, yet few epidemiological data exist for the general population in myanmar.201728056979
octaminomycins a and b, cyclic octadepsipeptides active against plasmodium falciparum.two new cyclic octadepsipeptides, octaminomycins a (1) and b (2), were isolated from a microbial metabolite fraction library of streptomyces sp. rk85-270 based on natural products plot screening. their structures were elucidated on the basis of hresims, 1d and 2d nmr spectroscopic data, and ms/ms experiments for sequence analysis. the absolute configurations of the constituent amino acid residues were determined by a combination of single-crystal x-ray diffraction and marfey's methodology. notab ...201728055207
complete attenuation of genetically engineered plasmodium falciparum sporozoites in human subjects.immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. however, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. we generated a genetically attenuated plasmodium falciparum (pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (pf p52(-)/p36(-)/sap1(-)). we then tested the safety and immunogenicity of the genetically engineered (pf gap3ko ...201728053159
association between polymorphisms in the pfmdr6 gene and ex vivo susceptibility to quinine in plasmodium falciparum parasites from dakar, senegal.polymorphisms and the overexpression of transporter genes, especially of the atp-binding cassette superfamily, have been involved in antimalarial drug resistance. the objective of this study was to use 77 senegalese plasmodium falciparum isolates to evaluate the association between the number of asn residues in the polymorphic microsatellite region of the plasmodium falciparum multidrug resistance 6 gene (pfmdr6) and the ex vivo susceptibility to antimalarials. a significant association was obse ...201728052850
safety of a fixed-dose combination of artesunate and amodiaquine for the treatment of uncomplicated plasmodium falciparum malaria in real-life conditions of use in côte d'ivoire.in many malaria-endemic, sub-saharan african countries, existing pharmacovigilance systems are not sufficiently operational to document reliably the safety profile of anti-malarial drugs. this study describes the implantation of a community-based pharmacovigilance system in côte d'ivoire and its use to document the safety of asaq winthrop(®) (artesunate-amodiaquine).201728049523
incidence and admission rates for severe malaria and their impact on mortality in africa.appropriate treatment of life-threatening plasmodium falciparum malaria requires in-patient care. although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. at present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access. consequently, the overall imp ...201728049519
genetic clustering and polymorphism of the merozoite surface protein-3 of plasmodium knowlesi clinical isolates from peninsular malaysia.the simian malaria parasite plasmodium knowlesi has been reported to cause significant numbers of human infection in south east asia. its merozoite surface protein-3 (msp3) is a protein that belongs to a multi-gene family of proteins first found in plasmodium falciparum. several studies have evaluated the potential of p. falciparum msp3 as a potential vaccine candidate. however, to date no detailed studies have been carried out on p. knowlesi msp3 gene (pkmsp3). the present study investigates th ...201728049516
evidence of non-plasmodium falciparum malaria infection in kédougou, sénégal.expanded malaria control efforts in sénégal have resulted in increased use of rapid diagnostic tests (rdt) to identify the primary disease-causing plasmodium species, plasmodium falciparum. however, the type of rdt utilized in sénégal does not detect other malaria-causing species such as plasmodium ovale spp., plasmodium malariae, or plasmodium vivax. consequently, there is a lack of information about the frequency and types of malaria infections occurring in sénégal. this study set out to bette ...201728049489
inhibition of placental mtor signaling provides a link between placental malaria and reduced birthweight.placental plasmodium falciparum malaria can trigger intervillositis, a local inflammatory response more strongly associated with low birthweight than placental malaria infection alone. fetal growth (and therefore birthweight) is dependent on placental amino acid transport, which is impaired in placental malaria-associated intervillositis. here, we tested the hypothesis that mechanistic target of rapamycin (mtor) signaling, a pathway known to regulate amino acid transport, is inhibited in placent ...201728049467
recrudescence of plasmodium falciparum in a primigravida after nearly 3 years of latency.we present a case of a primigravid woman who presented with plasmodium falciparum nearly 3 years after she last visited a malaria-endemic region. we review the literature to identify case reports of recrudescent p falciparum malaria during pregnancy, including those with prolonged latency. reports of recrudescence of p falciparum during pregnancy are limited. plasmodium falciparum infection can persist for years. recrudescence can occur with waning of immunity following departure from endemic ar ...201728044045
influence of the pfmdr1 gene on in vitro sensitivities of piperaquine in thai isolates of plasmodium falciparum.piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in thailand. the aim of this study was to determine the in vitro sensitivity of thai plasmodium falciparum isolates against piperaquine and the influence of the pfmdr1 gene on in vitro response. one hundred and thirty-seven standard laboratory and adapted thai isolates of p. falciparum were accessed for in vi ...201728044042
towards clinical development of a pfs48/45-based transmission blocking malaria vaccine.malaria is a devastating vector-borne disease caused by the plasmodium parasite, resulting in almost 0.5 million casualties per year. the parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. a vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. one of the leading ...201728043178
the prenylated proteome of plasmodium falciparum reveals pathogen-specific prenylation activity and drug mechanism-of-action.plasmodium parasites contain several unique membrane compartments in which prenylated proteins may play important roles in pathogenesis. protein prenylation has also been proposed as an antimalarial drug target because farnesyltransferase inhibitors cause potent growth inhibition of blood-stage plasmodium however, the specific prenylated proteins that mediate antimalarial activity have yet to be identified. given the potential for new parasite biology and elucidating drug mechanism-of-action, we ...201728040698
the rheopathobiology of plasmodium vivax and other important primate malaria parasites.our current understanding of how malaria parasites remodel their host red blood cells (rbcs) and ultimately cause disease is largely based on studies of plasmodium falciparum. in this review, we expand our knowledge to include what is currently known about pathophysiological changes to rbcs that are infected by non-falciparum malaria parasites. we highlight the potential folly of making generalizations about the rheology of malaria infection, and emphasize the need for more systematic studies in ...201728040374
synthesis, biological characterisation and structure activity relationships of aromatic bisamidines active against plasmodium falciparum.malaria is one of the most significant tropical diseases and remains a major challenge due to the lack of a broadly effective vaccine and parasite resistance to current drugs. this means there is a need for new drug candidates with novel modes of action. aromatic bisamidines, such as furamidine (db75), were initially developed as anti-trypanosoma agents however as clinical trials with furamidine highlighted potential side effects they were not pursued further in that setting. despite apparent cy ...201728038325
[evaluation of malaria rapid diagnostic test optimal-it® pldh along the plasmodium falciparum distribution limit in mauritania].performance of the malaria rapid diagnostic test (rdt) optimal-it® was evaluated in mauritania where malaria is low and dependent on a short transmission season. slide microscopy was considered as the reference method of diagnosis. febrile patients with suspected malaria were recruited from six health facilities, 3 urban and 3 rural, during two periods (december 2011 to february 2012, and august 2012 to march 2013). overall, 780 patients were sampled, with rdt and thick blood film microscopy res ...201728035638
crispr/cas9 mediated sequential editing of genes critical for ookinete motility in plasmodium yoelii.crispr/cas9 has been successfully adapted for gene editing in malaria parasites including plasmodium falciparum and plasmodium yoelii. however, the reported methods were limited to editing one gene at a time. in practice, it is often desired to modify multiple genetic loci in a parasite genome. here we describe a crispr/cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of p. yoelii using an improved single-vector system (pycm) we develope ...201728034675
force spectroscopy of the plasmodium falciparum vaccine candidate circumsporozoite protein suggests a mechanically pliable repeat region.the most effective vaccine candidate of malaria is based on the plasmodium falciparum circumsporozoite protein (csp), a major surface protein implicated in the structural strength, motility, and immune evasion properties of the infective sporozoites. it is suspected that reversible conformational changes of csp are required for infection of the mammalian host, but the detailed structure and dynamic properties of csp remain incompletely understood, limiting our understanding of its function in th ...201728031457
new derivatives of 7-chloroquinolin-4-amine with antiprotozoal activity.novel ω-aminoacyl and -alkyl derivatives of 7-chloroquinolin-4-amine were prepared and their structures confirmed by nmr spectroscopy. their antiprotozoal activities were examined in vitro against the sensitive nf54 strain as well as against the multiresistant k1 strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900). the results were compared with the activities of clinically used drugs. their antitrypanosomal activities were only moderate whereas their antiplasmo ...201728031151
towards a molecular architecture of the centrosome in toxoplasma gondii.toxoplasma gondii is the causative agent of toxoplasmosis. the pathogenicity of this unicellular parasite is tightly linked to its ability to efficiently proliferate within its host. tachyzoites, the fast dividing form of the parasite, divide by endodyogeny. this process involves a single round of dna replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. the successful completion of endodyogeny relies on the temporal and spatial coordination of a plethora of si ...201728026138
synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents.a series of novel fusidic acid (fa) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive nf54 and multidrug-resistant k1 strains of the malarial parasite plasmodium falciparum. most of these derivatives showed a 4-49 and 5-17-fold increase in activity against nf54 and ki strains, respectively, as compared to fa and had a good selectivity index. these deriva ...201728012840
comparison of functional assays used in the clinical development of a placental malaria vaccine.malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. plasmodium falciparum infected erythrocytes (ie) express var2csa that mediates binding to chondroitin sulphate a (csa) in the placenta. two var2csa-based vaccines for placental malaria are in clinical development. the purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines.201728012775
urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in gabon.an estimated 40 million women of childbearing age suffer from schistosomiasis. animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. to date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. this study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central africa. pregnant women attending antenatal clinics in fougamou and lambaréné, ...201728003151
novel inhibitors of plasmodium falciparum based on 2,5-disubstituted furans.phenotypic hts campaigns with a blood stage malaria assay have been used to discover novel chemotypes for malaria treatment with potential alternative mechanisms of action compared to existing agents. n(1)-(5-(3-chloro-4-fluorophenyl)furan-2-yl)-n(3),n(3)-dimethylpropane-1,3-diamine, 1 was identified as a modest inhibitor of p. falciparum nf54 (ic50 = 875 nm) with an apparent long plasma half-life after high dose oral administration to mice, although the compound later showed poor metabolic stab ...201728002775
polyoxygenated cyclohexenes and other constituents of cleistochlamys kirkii leaves.thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol b (3), cleistenechlorohydrins a (4) and b (5), cleistenediols a-f (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a meoh extract of the leaves of cleistochlamys kirkii. the purified metabolites were identified by nmr spectroscopic and mass spectrometric analy ...201728001067
a validated bioluminescence-based assay for the rapid determination of the initial rate of kill for discovery antimalarials.a future treatment for uncomplicated malaria will contain at least one component that exerts a rapid rate of kill. we describe here the validation and application of a simple, robust and rapid bioluminescence-based assay for the determination of the initial rate of kill in intra-erythrocytic asexual stages of plasmodium falciparum .201727999014
intramolecular diaza-diels-alder protocol: a new diastereoselective and modular one-step synthesis of constrained polycyclic frameworks.phenotype-based screening of diverse compound collections generated by privileged substructure-based diversity-oriented synthesis (pdos) is considered one of the prominent approaches in the discovery of novel drug leads. however, one key challenge that remains is the development of efficient and modular synthetic routes toward the facile access of privileged small-molecule libraries with skeletal and stereochemical complexity and drug-like properties. in this regard, a novel and diverse one-pot ...201727997727
burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration.burkitt lymphoma (bl) is a malignant disease, which is frequently found in areas with holoendemic plasmodium falciparum malaria. we have previously found that the var2csa protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofcs is absent in other non-malignant tissues and thus var2csa generally facilitates parasite sequestration and accumulation in pregnant women. in this study, we show that the specific receptor for var2csa, the oncofet ...201727997697
nanomolar antimalarial agents against chloroquine-resistant plasmodium falciparum from medicinal plants and their structure-activity relationships.inspired by the discovery of the antimalarial drug artemisinin from a traditional chinese medicine (tcm), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the dd2 chloroquine-resistant strain of the malaria parasite plasmodium falciparum. these compounds were mainly isolated from plants of the chloranthus genus, many species of which are named "sikuaiwa" in tcm and have long been used to treat malaria. the compounds consisted of 41 sesquiterpeno ...201727997206
high rate of treatment failures in nonimmune travelers treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in sweden: retrospective comparative analysis of effectiveness and case series.artemisinin-based combination therapy (act) is the first-line treatment of plasmodium falciparum malaria. since the introduction of artemether-lumefantrine (al) for treatment of uncomplicated malaria in sweden, treatment failures have been reported in adults.201727986683
evaluation of the parasight platform for malaria diagnosis.the world health organization estimates that nearly 500 million malaria tests are performed annually. while microscopy and rapid diagnostic tests (rdts) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. here we present the results from two clinical studies on the commercially available version of this technology, the sight diagnostics par ...201727974542
prevention and control of malaria in pregnancy - new threats, new opportunities?over 100 million women and their babies are at risk of malaria in pregnancy each year. malaria prevention in pregnancy relies on long-lasting insecticidal nets (llins), and, in africa, intermittent preventive treatment in pregnancy (iptp). increasing resistance of malaria parasites to sulfadoxine-pyrimethamine, the only drug endorsed for iptp, and increasing mosquito resistance to pyrethroids used in llins, threaten the efficacy of these proven strategies, while operational challenges restrict t ...201727973923
discovery of a pcaf bromodomain chemical probe.the p300/cbp-associated factor (pcaf) and related gcn5 bromodomain-containing lysine acetyl transferases are members of subfamily i of the bromodomain phylogenetic tree. iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine-based l-45 (dubbed l-moses) as the first potent, selective, and cell-active pcaf bromodomain (brd) inhibitor. synthesis from readily available (1r,2s)-(-)-norephedrine furnished l-45 in enantiopure form. ...201727966810
contribution of real-time pcr to plasmodium species identification and to clinical decisions: a nationwide study in a non-endemic setting.treatment choice for patients with malaria in israeli hospitals is based on microscopy and rapid diagnostic tests (rdts). here, we demonstrate the cumulative value of real-time polymerase chain reaction (pcr) in optimizing the treatment of malaria. between january 2009 and december 2015, 451 samples from 357 patients were tested in our laboratory using a real-time pcr assay. hospital laboratory results (without real-time pcr) were compared to those obtained in our laboratory. a total of 307 pati ...201727966198
plasmodium vivax controlled human malaria infection - progress and prospects.modern controlled human malaria infection (chmi) clinical trials have almost entirely focussed on plasmodium falciparum, providing a highly informative means to investigate host-pathogen interactions as well as assess potential new prophylactic and therapeutic interventions. however, in recent years, there has been renewed interest in plasmodium vivax, with chmi models developed by groups in colombia, the usa, and australia. this review summarizes the published experiences, and examines the adva ...201727956060
changes in malaria epidemiology in africa and new challenges for elimination.although the burden of plasmodium falciparum malaria is gradually declining in many parts of africa, it is characterized by spatial and temporal variability that presents new and evolving challenges for malaria control programs. reductions in the malaria burden need to be sustained in the face of changing epidemiology whilst simultaneously tackling significant pockets of sustained or increasing transmission. large-scale, robust surveillance mechanisms that measure rather than estimate the actual ...201727939610
epcr and malaria severity: the center of a perfect storm.severe malaria due to plasmodium falciparum infection causes nearly half a million deaths per year. the different symptomatology and disease manifestations among patients have hampered understanding of severe malaria pathology and complicated efforts to develop targeted disease interventions. infected erythrocyte sequestration in the microvasculature plays a critical role in the development of severe disease, and there is increasing evidence that cytoadherent parasites interact with host factors ...201727939609
proteomic identification and analysis of arginine-methylated proteins of plasmodium falciparum at asexual blood stages.plasmodium falciparum undergoes a tightly regulated developmental process in human erythrocytes, and recent studies suggest an important regulatory role of post-translational modifications (ptms). as compared with plasmodium phosphoproteome, little is known about other ptms in the parasite. in the present study, we performed a global analysis of asexual blood stages of plasmodium falciparum to identify arginine-methylated proteins. using two different methyl arginine-specific antibodies, we immu ...201727933903
risk of drug resistance in plasmodium falciparum malaria therapy-a systematic review and meta-analysis.plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. although a number of studies have reported the emergence of drug resistance in different therapies for p. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. this research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. relevant original randomized control ...201728028628
severe unresolving plasmodium falciparum malaria following artemisinin combination therapy: emergence of drug resistance in saudi arabia.a 5-year-old female child presented with fever of 1-week duration after visiting a malaria endemic zone without antimalarial prophylaxis. the patient presented with respiratory distress, decreased level of consciousness and high-grade fever. an elevated parasitaemia reaching 800,000/μl was observed. antimalarial therapy was initiated with artesunate being administered intravenous (iv) along with iv clindamycin. contrary to the expectations, there was no resolution of fever. following a week of u ...201727934844
in vitro sensitivity pattern of chloroquine and artemisinin in plasmodium falciparum.artemisinin (art) and its derivatives form the mainstay of antimalarial therapy. emergence of resistance to them poses a potential threat to future malaria control and elimination on a global level. it is important to know the mechanism of action of drug and development of drug resistance. we put forwards probable correlation between the mode of action of chloroquine (cq) and art. modified trophozoite maturation inhibition assay, who mark iii assay and molecular marker study for cq resistance at ...201727934832
structural dynamics of casein kinase i (cki) from malarial parasite plasmodium falciparum (isolate 3d7): insights from theoretical modelling and molecular simulations.the protein kinases (pks), belonging to serine/threonine kinase (stks), are important drug targets for a wide spectrum of diseases in human. among protein kinases, the casein kinases (cks) are vastly expanded in various organisms, where, the malarial parasite plasmodium falciparum possesses a single member i.e., pfcki, which can phosphorylate various proteins in parasite extracts in vitro condition. but, the structure-function relationship of pfcki and dynamics of atp binding is yet to be unders ...201727923179
high-throughput screening and prediction model building for novel hemozoin inhibitors using physicochemical properties.it is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by plasmodium falciparum parasites. in this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. an in vitro colorimetric high-throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. the physicochemical properties of po ...201727919903
significant divergence in sensitivity to antimalarial drugs between neighboring plasmodium falciparum populations along the eastern border of myanmar.malaria parasites in different areas where malaria is endemic display different levels of resistance to antimalarial drugs as the result of varied drug use histories. to provide updated knowledge of drug sensitivities during the malaria elimination phase in southeast asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted plasmodium falciparum isolates from two eastern border regions (wa and kachin) of myanmar to 10 drugs. despite their close proxim ...201727919892
antiparasitic and disease-modifying activity of nyctanthes arbor-tristis linn. in malaria: an exploratory clinical study.an unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. a scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. an ayurvedic plant nyctanthes arbor-tristis linn. - (parijat) is being used in clinical practice and had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study.201727914754
immunogenicity and malaria transmission reducing potency of pfs48/45 and pfs25 encoded by dna vaccines administered by intramuscular electroporation.pfs48/45 and pfs25 are leading candidates for the development of plasmodium falciparum transmission blocking vaccines (tbv). expression of pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. however, it has been challenging to produce a fully folded, functionally active pfs48/45, using various protein expression platforms. in this study, we demonstrate that full-length pfs48/45 encoded by dn ...201727912985
antimalarial activity of novel 4-aminoquinolines active against drug resistant strains.in the present study we have synthesized a new class of 4-aminoquinolines and evaluated against plasmodium falciparum in vitro (3d7-sensitive strain & k1-resistant strain) and plasmodium yoelii in vivo (n-67 strain). among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against k1 strain as compared to cq. in addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against n-67 strain wh ...201727908538
plasmodium vivax vaccine research - we've only just begun.plasmodium vivax parasites cause the majority of malaria cases outside africa, and are increasingly being acknowledged as a cause of severe disease. the unique attributes of p. vivax biology, particularly the capacity of the dormant liver stage, the hypnozoite, to maintain blood-stage infections even in the absence of active transmission, make blood-stage vaccines particularly attractive for this species. however, p. vivax vaccine development remains resolutely in first gear, with only a single ...201727899329
evaluation of immunoglobulin g responses to plasmodium falciparum and plasmodium vivax in malian school children using multiplex bead assay.malaria serology through assaying for igg against plasmodium spp. antigens provides evidence into the infection history for an individual. the multiplex bead assay (mba) allows for detection of igg against multiple plasmodium spp., and can be especially useful in many regions where plasmodium falciparum is of primary clinical focus, but other species are co-endemic. dried blood spots were collected from 805 malian children attending 42 elementary schools in the regions of mopti, sikasso, kouliko ...201727895279
examination of antibody responses as a measure of exposure to malaria in the indigenous batwa and their non-indigenous neighbors in southwestern uganda.understanding variations in malaria transmission and exposure is critical to identify populations at risk and enable better targeting of interventions. the indigenous batwa of southwestern uganda have a disproportionate burden of malaria infection compared with their non-indigenous neighbors. to better understand the individual- and community-level determinants of malaria exposure, a seroepidemiological study was conducted in 10 local council cells in kanungu district, uganda, in april 2014. the ...201727895271
plasmodium knowlesi and human malaria parasites in khan phu, vietnam: gametocyte production in humans and frequent co-infection of mosquitoes.four species of malaria parasite, plasmodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium knowlesi infect humans living in the khanh phu commune, khanh hoa province, vietnam. the latter species also infects wild macaque monkeys in this region. in order to understand the transmission dynamics of the three species, we attempted to detect gametocytes of the three species in the blood of infected individuals, and sporozoites in the salivary glands of mosquitoes from the same regi ...201727894375
trafficking of pfexp1 to the parasitophorous vacuolar membrane of plasmodium falciparum is independent of protein folding and the ptex translocon.having entered the mature human erythrocyte, the malaria parasite survives and propagates within a parasitophorous vacuole, a membrane-bound compartment separating the parasite from the host cell cytosol. the bounding membrane of this vacuole, referred to as the parasitophorous vacuolar membrane (pvm), contains parasite-encoded proteins, but how these membrane proteins are trafficked to the pvm remains unknown. here, we have studied the trafficking of pfexp1 to the pvm. we find that trafficking ...201727892646
cord blood igg and the risk of severe plasmodium falciparum malaria in the first year of life.young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. here, we investigated whether cord blood igg to plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at diff ...201727890694
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