Publications

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an ultrasensitive enzyme-free electrochemical immunosensor based on redox cycling amplification using methylene blue.we report a new enzyme-free electrochemical sensor for ultrasensitive measurements of protein biomarkers in plasma and whole blood samples based on a unique electrochemical-chemical-chemical (ecc) redox cycling signal amplification scheme. this scheme uses methylene blue (mb) as a redox indicator which undergoes an endergonic reaction with ru(nh3)6(3+) and a highly exergonic reaction with tris(2-carboxyethyl)phosphine (tcep). this approach offers improved detection sensitivity and sensor stabili ...201728831485
red blood cells release microparticles containing human argonaute 2 and mirnas to target genes of plasmodium falciparum.red blood cells (rbcs) are known to function as a refuge for providing food resources and as a shelter against the host's immune system after malaria parasite (plasmodium) infection. recent studies have reported significant production of extracellular vesicles (microparticles, mps) in the circulation of malaria patients. however, it is unclear how these extracellular vesicles are generated and what their biological functions are. in this study, we isolated the mps from a culture medium of normal ...201728831191
naturally acquired antibody response to plasmodium falciparum describes heterogeneity in transmission on islands in lake victoria.as markers of exposure anti-malaria antibody responses can help characterise heterogeneity in malaria transmission. in the present study antibody responses to plasmodium falciparum ama-1, msp-119 and csp were measured with the aim to describe transmission patterns in meso-endemic settings in lake victoria. two cross-sectional surveys were conducted in lake victoria in january and august 2012. the study area comprised of three settings: mainland (ungoye), large island (mfangano) and small islands ...201728831122
immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural plasmodium vivax exposure.plasmodium vivax is the most geographically widespread malaria species and codominates with plasmodium falciparum, the deadliest form of the malaria parasite. for the last few years, the number of vivax malaria cases has increased, but vivax malaria is still considered a neglected disease. during the blood stages of their life cycle, p. vivax parasites export several hundred proteins into host red blood cells. some of these exported proteins have been discovered and studied for use as a blood-st ...201728830553
histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in plasmodium falciparum.the dynamics of histone modifications in plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (idc) of p. falciparum.201728830512
sustained high cure rate of artemether-lumefantrine against uncomplicated plasmodium falciparum malaria after 8 years of its wide-scale use in bagamoyo district, tanzania.we assessed the temporal trend of artemether-lumefantrine (al) cure rate after 8 years of its wide-scale use for treatment of uncomplicated plasmodium falciparum malaria from 2006 to 2014 in bagamoyo district, tanzania. trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. patients with acute uncomplicated p. falciparum malaria were enrolled, treated with standard al regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days ...201728829723
production and characterization of extracellular vesicles in malaria.growing attention is drawn toward the role of extracellular vesicles (evs) in infectious diseases. evs, which are small vesicles released by cells, are involved in cellular communication, immune regulation, and pathogenesis. evs act as messenger carrying functional cargoes, including rna, dna, lipids and proteins from a donor cell to regulate the function of a recipient cell. in malaria, evs play a key role in regulating the progression from the blood to the transmission stage by promoting the s ...201728828673
mepicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis.the emergence of plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. mepicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (mep) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (dxr). here we describe rcb-185, a lipophilic prodrug with nanomolar activity against asexual parasites. grow ...201728827774
small molecule inhibition of apicomplexan ftsh1 disrupts plastid biogenesis in human pathogens.the malaria parasite plasmodium falciparum and related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. derived from secondary endosymbiosis, the apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import and organelle inheritance during parasite replication. these critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. we used an innovative screen to ...201728826494
longitudinal study of changes in γδ t cells and cd4(+) t cells upon asymptomatic malaria infection in indonesian children.both γδ t cells and cd4(+) t cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. therefore, we followed up asymptomatic children living in an area endemic for malaria in indonesia for 21 months. the percentage of γδ t cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. infected children also had higher ...201728821806
spatial clustering of patent and sub-patent malaria infections in northern namibia: implications for surveillance and response strategies for elimination.reactive case detection (racd) around passively detected malaria cases is a strategy to identify and treat hotspots of malaria transmission. this study investigated the unproven assumption on which this approach is based, that in low transmission settings, infections cluster over small scales.201728820883
house structure is associated with plasmodium falciparum infection in a low-transmission setting in southern zambia.house structure may influence the risk of malaria by affecting mosquito entry and indoor resting. identification of construction features associated with protective benefits could inform vector control approaches, even in low-transmission settings. we examined the association between house structure and malaria prevalence in a cross-sectional analysis of 2,788 children and adults residing in 866 houses in a low-transmission area of southern province, zambia, over the period 2008-2012. houses wer ...201728820722
quality testing of artemisinin-based antimalarial drugs in myanmar.artemisinin-based combination therapies are the frontline treatment of plasmodium falciparum malaria. the circulation of falsified and substandard artemisinin-based antimalarials in southeast asia has been a major predicament for the malaria elimination campaign. to provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of myanmar. the quality of these drugs in terms of their artemisinin de ...201728820713
performance of a high-sensitivity rapid diagnostic test for plasmodium falciparum malaria in asymptomatic individuals from uganda and myanmar and naive human challenge infections.sensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination. the performance of a new alere™ malaria ag p.f ultra sensitive rapid diagnostic test (urdt) was compared with the currently available sd bioline malaria ag p.f rdt in blood specimens from asymptomatic individuals in nagongera, uganda, and in a karen village, myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from fo ...201728820709
malaria in the guangxi zhuang autonomous region in china: a twelve-year surveillance data study.the incidence of an indigenous malaria, defined as malaria acquired by a local mosquito transmission, declined from 2004 to 2015 in the guangxi zhuang autonomous region. however, imported malaria, defined as malaria acquired from other endemic regions outside of china, has been increasing in the region, as in the rest of the country, particularly the disease caused by plasmodium falciparum. a retrospective study was conducted to explore malaria-endemic characteristics in guangxi during the 2004- ...201728820683
case report: a case of plasmodium falciparum hrp2 and hrp3 gene mutation in bangladesh.several species of plasmodium are responsible for causing malaria in humans. proper diagnoses are crucial to case management, because severity and treatment varies between species. diagnoses can be made using rapid diagnostic tests (rdts), which detect plasmodium proteins. plasmodium falciparum causes the most virulent cases of malaria, and p. falciparum histidine-rich protein 2 (pfhrp2) is a common target of falciparum malaria rdts. here we report a case in which a falciparum malaria patient in ...201728820682
[evaluation of the onsite malaria rapid test performance in miandrivazo, madagascar].the performance of the malaria rapid diagnostic test onsite-for detecting pan specific pldh and plasmodium falciparum specific hrp2 - was assessed during the malaria transmission peak period in miandrivazo, in the southwestern part of madagascar from april 20 to may 6, 2010. at the laboratory, the quality control onsite malaria rapid test according to the who/tdr/find method demonstrated that the test had good sensitivity. of the 218 onsite tests performed at the miandrivazo primary health cente ...201728819735
fbn30 in wild anopheles gambiae functions as a pathogen recognition molecule against clinically circulating plasmodium falciparum in malaria endemic areas in kenya.malaria is a worldwide health problem that affects two-thirds of the world population. plasmodium invasion of anopheline mosquitoes is an obligatory step for malaria transmission. however, mosquito-malaria molecular interactions in nature are not clear. a genetic variation within mosquito fibrinogen related-protein 30 (fbn30) was previously identified to be associated with plasmodium falciparum infection in natural anopheles gambiae populations at malaria endemic areas in kenya, and reducing fbn ...201728819256
presence of quintuple dhfr n51, c59, s108 - dhps a437, k540 mutations in plasmodium falciparum isolates from pregnant women and the general population in nanoro, burkina faso.sulphadoxine-pyrimethamine (sp) is only used for intermittent preventive treatment during pregnancy (iptp) in most sub-saharan african countries. however, there are concerns about the efficacy of iptp-sp because of increasing resistance. combinations of point mutations in the dhps and dhfr genes of plasmodium falciparum are associated with sp resistance, in particular the quintuple dhfr (n51, c59, s108) - dhps (codons a437, k540) mutant. in nanoro, burkina faso, filter paper samples from pregnan ...201728818675
a new method for sequencing the hypervariable plasmodium falciparum gene var2csa from clinical samples.var2csa, a member of the plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) family, mediates the binding of p. falciparum-infected erythrocytes to chondroitin sulfate a, a surface-associated molecule expressed in placental cells, and plays a central role in the pathogenesis of placental malaria. var2csa is a target of naturally acquired immunity and, as such, is a leading vaccine candidate against placental malaria. this protein is very polymorphic and technically challenging to seque ...201728818101
do the venous blood samples replicate malaria parasite densities found in capillary blood? a field study performed in naturally-infected asymptomatic children in cameroon.the measure of new drug- or vaccine-based approaches for malaria control is based on direct membrane feeding assays (dmfas) where gametocyte-infected blood samples are offered to mosquitoes through an artificial feeder system. gametocyte donors are identified by the microscopic detection and quantification of malaria blood stages on blood films prepared using either capillary or venous blood. however, parasites are known to sequester in the microvasculature and this phenomenon may alter accurate ...201728818084
isolation of the new antiplasmodial butanolide malleastrumolide a from a malleastrum sp. (meliaceae) from madagascar.an extract of a malleastrum sp. (meliaceae) collected in madagascar by the madagascar international cooperative biodiversity group was found to have antimalarial activity, with an ic50 value between 2.5 and 5 μg/ml. after purification by liquid-liquid partition, chromatography on a diaion open column, c-18 spe and c-18 reverse phase hplc, the new butanolide malleastrumolide a was isolated. the structure of malleastrumolide a was determined by mass spectrometry, nmr and ecd. the double bond posit ...201728817228
modelling the benefits of long-acting or transmission-blocking drugs for reducing plasmodium falciparum transmission by case management or by mass treatment.anti-malarial drugs are an important tool for malaria control and elimination. alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. different compounds potentially have different impacts on transmission-with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. the aim was to quantify the relative benefit of ...201728814310
synthesis and evaluation of asymmetric acyclic nucleoside bisphosphonates as inhibitors of plasmodium falciparum and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferase.acyclic nucleoside bisphosphonates (anbps) have previously been shown to be good inhibitors of human hypoxanthine-guanine phosphoribosyltransferase (hgprt) and plasmodium falciparum (pf) hypoxanthine-guanine-xanthine phosphoribosyltransferase (pfhgxprt). on the basis of this scaffold, a new series of anbps was synthesized. one of these new anbps, [3-(guanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methylphosphonic acid, exhibited ki values of 6 and 70 nm for human hgprt and pf hgxprt, respect ...201728813147
a variant pfcrt isoform can contribute to plasmodium falciparum resistance to the first-line partner drug piperaquine.current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout asia of plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (ppq) in cambodia. using zinc finger nuclease-based gene editing, we report that addition of the c101f mutation to the chloroquine (cq) resistance-conferring pfcrt dd2 isoform common to asia can confer ppq resistance to c ...201728487425
binding of plasmodium falciparum to cd36 can be shielded by the glycocalyx.plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. it was investigated if the cellular glycocalyx affects the binding of p. falciparum-infected erythrocytes to cd36 in vitro.201728486940
antimalarial silver and gold nanoparticles: green synthesis, characterization and in vitro study.in the present study, we are reporting antimalarial potential of silver (agnps) and gold (aunps) nanoparticles synthesized by leaf and bark extract of syzygium jambos (l.) alston (myrtaceae). aunps and agnps obtained by both the extracts were characterized using uv-vis spectroscopy, zeta potential, transmission electron microscopy (tem), x-ray diffraction (xrd), and fourier transform infrared spectroscopy (ftir). nmr and ftir spectra indicate that the saccharides and phenolics present in the s. ...201728486189
recruitment of human c1 esterase inhibitor controls complement activation on blood stage plasmodium falciparum merozoites.the complement system is a front-line defense system that opsonizes and lyses invading pathogens. to survive, microbes exposed to serum must evade the complement response. to achieve this, many pathogens recruit soluble human complement regulators to their surfaces and hijack their regulatory function for protection from complement activation. c1 esterase inhibitor (c1-inh) is a soluble regulator of complement activation that negatively regulates the classical and lectin pathways of complement t ...201728484054
green-synthesized cds nano-pesticides: toxicity on young instars of malaria vectors and impact on enzymatic activities of the non-target mud crab scylla serrata.currently, nano-formulated mosquito larvicides have been widely proposed to control young instars of malaria vector populations. however, the fate of nanoparticles in the aquatic environment is scarcely known, with special reference to the impact of nanoparticles on enzymatic activity of non-target aquatic invertebrates. in this study, we synthesized cds nanoparticles using a green protocol relying on the cheap extract of valoniopsis pachynema algae. cds nanoparticles showed high toxicity on you ...201728482328
role of myd88-adaptor-like gene polymorphism rs8177374 in modulation of malaria severity in the pakistani population.the present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of plasmodium vivax and plasmodium falciparum.201728482182
regulation of pfemp1-var2csa translation by a plasmodium translation-enhancing factor.pregnancy-associated malaria commonly involves the binding of plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate a (csa) through the pfemp1-var2csa protein. var2csa is translationally repressed by an upstream open reading frame. in this study, we report that the p. falciparum translation enhancing factor (ptef) relieves upstream open reading frame repression and thereby facilitates var2csa translation. var2csa protein levels in var2csa-transcribing parasites are depende ...201728481333
artemether-lumefantrine and dihydroartemisinin-piperaquine exert inverse selective pressure on plasmodium falciparum drug sensitivity-associated haplotypes in uganda.altered sensitivity to multiple antimalarial drugs is mediated by polymorphisms in pfmdr1, which encodes the plasmodium falciparum multidrug resistance transporter. in africa the n86y and d1246y polymorphisms have been shown to be selected by treatment, with artemether-lumefantrine (al) and dihydroartemisinin-piperaquine (dp) selecting for wild-type and mutant alleles, respectively. however, there has been little study of pfmdr1 haplotypes, in part because haplotype analyses are complicated by m ...201728480232
anti-plasmodial and chloroquine resistance suppressive effects of embelin.emergence of chloroquine (cq) resistance among different strains of plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. this urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect.201728479726
glutathione and thioredoxin systems of the malaria parasite plasmodium falciparum: partners in crime?in p. falciparum, antioxidant proteins of the glutathione and thioredoxin systems are compartmentalized. some subcellular compartments have only a partial complement of these proteins. this lack of key anti-oxidant proteins in certain sub-cellular compartments might be compensated by functional complementation between these systems. by assessing the cross-talk between these systems, we show for the first time, that the glutathione system can reduce thioredoxins that are poor substrates for thior ...201728479253
accelerated and long term stability study of pfs25-epa conjugates adjuvanted with alhydrogel®.pfs25, a plasmodium falciparum surface protein expressed during zygote and ookinete stages in infected mosquitoes, is a lead transmission-blocking vaccine candidate against falciparum malaria. to enhance immunogenicity, recombinant pfs25 was chemically conjugated to recombinant nontoxic pseudomonas aeruginosa exoprotein a (repa) in conformance with current good manufacturing practices (cgmp), and formulated with the alum adjuvant alhydrogel. in order to meet the regulatory requirements for a pha ...201728479180
evaluation of the utility value of three diagnostic methods in the detection of malaria parasites in endemic area.malaria is a debilitating disease with high morbidity and mortality in africa, commonly caused by different species of the genus plasmodium in humans. misdiagnosis is a major challenge in endemic areas because of other disease complications and technical expertise of the medical laboratory staff. microscopic method using giemsa-stained blood film has been the mainstay of diagnosis of malaria. however, since 1993 when rapid diagnostic test (rdt) kits were introduced, they have proved to be effect ...201728477621
development and in vitro evaluation of oxytetracycline-loaded pmma nanoparticles for oral delivery against anaplasmosis.poly-methyl methacrylate (pmma) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non-toxicity and cost effectiveness. in this investigation, oxytetracycline-loaded pmma nanoparticles were prepared using nano-precipitation method for the treatment of anaplasmosis. the prepared nanoparticles were characterised using dynamic light scattering (dls), atomic force microscopy (afm), differential scanning calorimetry (dsc) ...201728476972
malaria pigment stimulates chemokine production by human microvascular endothelium.severe falciparum malaria is characterized by the sequestration of infected erythrocytes and leukocyte recruitment in the microvasculature, resulting in impaired blood flow and metabolic disturbances. which parasite products cause chemokine production, thus contributing to the strong host inflammatory response and cellular recruitment are not well characterized. here, we studied haemozoin (hz), the end-product of haem, a ferriprotoporphyrin-ix crystal bound to host and parasite lipids, dna, and ...201728476599
plasmodium falciparum histidine-rich protein ii causes vascular leakage and exacerbates experimental cerebral malaria in mice.a devastating complication of plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. p. falciparum produces a protein called histidine-rich protein ii (hrpii) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. using a human cerebral microvascular endothelial barrier model, we previously found that hrpii activates the endothelial cell inf ...201728475625
sybr(®) green i-based fluorescence assay to assess cell viability of malaria parasites for routine use in compound screening.owing to its fast and reliable assessment of parasite growth, the sybr(®) green i-based fluorescence assay is widely used to monitor drug susceptibility of malaria parasites. its particular advantages are that it is a simple, one-step procedure and very cost-effective making it especially suited for high through put screening of newly developed drugs and drug combinations. here we describe a sybr(®) green i-based fluorescence assay protocol to be used for routine screening of compounds and extra ...201728470521
heterozygous hbac but not hbas is associated with higher newborn birthweight among women with pregnancy-associated malaria.pregnancy-associated malaria (pam) is associated with poor pregnancy outcomes. hemoglobin s (hbs) and hemoglobin c (hbc) mutations are frequently encountered in malaria-endemic areas of africa, where they protect children from severe and uncomplicated plasmodium falciparum malaria. however, scant epidemiological data exist on the impact of these hb variants on pam. a prospective cohort of 635 beninese pregnant women was recruited before 24 weeks of gestational age and followed until the end of p ...201728469130
oxidative stress in malaria and artemisinin combination therapy: pros and cons.artemisinin-based combination therapy (act) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. act combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug. although the exact mechanisms of action of artemisinins are not well understood, several studies have proposed multiple cellular targets of artemisinins with involvement of reactive oxygen species (ros). mo ...201728467668
sequence variation in plasmodium falciparum histidine rich proteins 2 and 3 in indian isolates: implications for malaria rapid diagnostic test performance.commercial malaria rapid diagnostic tests (rdts) detect p. falciparum histidine rich protein 2 (pfhrp2) and cross react with pfhrp3, a structural homologue. here, we analysed natural variations in pfhrp2 and pfhrp3 sequences from indian isolates and correlated these variations with rdt reactivity. a total 1392 p. falciparum positive samples collected from eight endemic states were pcr amplified for pfhrp2 and pfhrp3 genes and were sequenced. the deduced protein sequences were analysed for repeat ...201728465622
in-vivo efficacy of chloroquine to clear asymptomatic infections in mozambican adults: a randomized, placebo-controlled trial with implications for elimination strategies.recent reports regarding the re-emergence of parasite sensitivity to chloroquine call for a new consideration of this drug as an interesting complementary tool in malaria elimination efforts, given its good safety profile and long half-life. a randomized (2:1), single-blind, placebo-controlled trial was conducted in manhiça, mozambique, to assess the in-vivo efficacy of chloroquine to clear plasmodium falciparum (pf) asymptomatic infections. primary study endpoint was the rate of adequate and p ...201728465550
private sector opportunities and threats to achieving malaria elimination in the greater mekong subregion: results from malaria outlet surveys in cambodia, the lao pdr, myanmar, and thailand.the aim of this paper is to review multi-country evidence of private sector adherence to national regulations, guidelines, and quality-assurance standards for malaria case management and to document current coverage of private sector engagement and support through actwatch outlet surveys implemented in 2015 and 2016.201728464945
the development of sexual stage malaria gametocytes in a wave bioreactor.blocking malaria gametocyte development in rbcs or their fertilization in the mosquito gut can prevent infection of the mosquito vector and passage of disease to the human host. a 'transmission blocking' strategy is a component of future malaria control. however, the lack of robust culture systems for producing large amounts of plasmodium falciparum gametocytes has limited our understanding of sexual-stage malaria biology and made vaccine or chemotherapeutic discoveries more difficult.201728464929
malaria epidemiology in an area of stable transmission in tribal population of jharkhand, india.malaria remains an important health problem in india with approximately 1 million cases in 2014. of these, 7% occurred in the jharkhand state mainly in the tribal population.201728464875
volatile organic compounds associated with plasmodium falciparum infection in vitro.in order to identify new ways to prevent transmission of vector-borne diseases such as malaria, efforts have been made to understand how insects are attracted to humans. vector-host interaction studies have shown that several volatile compounds play an important role in attracting mosquitoes to human targets. a headspace solid-phase micro-extraction/gas chromatography-mass spectrometry (hspme gc-ms) analysis of the volatile organic composition of extracellular vesicles (evs) and supernatants of ...201728464853
membrane and luminal proteins reach the apicoplast by different trafficking pathways in the malaria parasite plasmodium falciparum.the secretory pathway in plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. the latter can occur via the er or the er-golgi route. here, we study these three routes using proteins erythrocyte membrane protein-1 (pfemp1), acyl carrier protein (acp) and glutathione peroxidase-like thioredoxin peroxidase (pftpxgl) and inhibitors of vesicular transport. as expected, the g protein-dependent vesicular fusion inhibitor al ...201728462015
evidence of strain structure in plasmodium falciparum var gene repertoires in children from gabon, west africa.existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. this prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. for plasmodium falciparum, strain theory has been spe ...201728461509
guanylthiourea derivatives as potential antimalarial agents: synthesis, in vivo and molecular modelling studies.guanylthiourea (gtu) derivatives were identified as possible anti-malarial agents, recently, using in vitro studies on plasmodium falciparum. this article gives an account of the in vivo anti-malarial activity of gtu derivatives against experimental rodent malaria. a total of 20 synthesized gtu derivatives were evaluated for in vivo antimalarial activity, out of which six showed encouraging results; one compound appeared to have curative potential. molecular docking and molecular dynamics analys ...201728460309
baseline in vivo, ex vivo and molecular responses of plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in colombia.colombia began using artemisinin-based combination therapies for the treatment of uncomplicated plasmodium falciparum malaria in 2006. it is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. the aim of this study was to establish a susceptibility baseline of p. falciparum to artemether-lumefantrine using three monitoring tools.201728460112
a combined strategy for screening a clustered mobile population returning from highly endemic areas for plasmodium falciparum.early and accurate diagnosis of imported malaria cases in clusters is crucial for protecting the health of patients and local populations, especially confirmed parasitic persons who are asymptomatic.201728459219
polymyxin b inhibits the chaperone activity of plasmodium falciparum hsp70.heat shock protein 70 (hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. hsp70s are also implicated in the survival and pathogenicity of malaria parasites. the main agent of malaria, plasmodium falciparum, expresses six hsp70s. of these, two (pfhsp70-1 and pfhsp70-z) localize to the parasite cytosol. previously conducted gene knockout studies suggested that pfhsp70-z is essential, and it has been demonstrated that small-molecule inhibitors targeting pfhsp70-1 ...201728455613
two new antimalarial quassinoid derivatives from the stems of brucea javanica.phytochemical investigation of the stems from brucea javanica led to the isolation of two new quassinoids, brujavanol c (1) and brujavanol d (2), together with six known compounds (3-8). the chemical structures were elucidated by means of various spectroscopic methods. all the isolated compounds were evaluated for antimalarial activity against plasmodium falciparum and compounds 6 and 7 exhibited the most potent activity against the k1 strain, with ic50 values of 1.41 and 1.06 μm, respectively.201728455552
longitudinal genomic surveillance of plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance.artemisinin-based combination therapies are the first line of treatment for plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in southeast asia over the past decade. mutations in the kelch13 gene have been implicated in this resistance. we used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. we retrospectively sequenced the genomes of 194 p. falciparum isolates from fiv ...201728454557
increase in the prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in plasmodium falciparum isolates collected from early to late pregnancy in nanoro, burkina faso.pregnant women are a high-risk group for plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy (iptp-sp) is widely implemented to prevent these negative effects of malaria. however, resistance against sp by p. falciparum may decrease efficacy of iptp-sp. combinations of point mutations in the dhps (codons a437, k540) and dhfr genes ...201728454537
dynamic interactions of plasmodium spp. with vascular endothelium.plasmodial species are protozoan parasites that infect erythrocytes. as such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. the host-parasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. plasmodium falciparum, the causative agent of the most sever ...201728452684
prophylactic efficacy of primaquine for preventing plasmodium falciparum and plasmodium vivax parasitaemia in travelers: a meta-analysis and systematic review.with increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. the choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. to fill the gap, this systematic review and meta-analysis study was carried out.201728450185
absence of association between polymorphisms in the k13 gene and the presence of plasmodium falciparum parasites at day 3 after treatment with artemisinin derivatives in senegal.in 2006, the senegalese national malaria control programme recommended artemisinin-based combination therapy as first-line treatment for uncomplicated malaria. in addition, intravenous (i.v.) injection of artesunate and artemether has gradually replaced quinine for the treatment of severe malaria. mutations in the propeller domain of the kelch 13 gene (k13-propeller, pf3d71343700), such as y493h, r539t, i543t and c580y, were recently associated with in vivo and in vitro resistance to artemisinin ...201728450175
recent advances in use of silver nanoparticles as antimalarial agents.malaria is one of the most common infectious diseases, which has become a great public health problem all over the world. ineffectiveness of available antimalarial treatment is the main reason behind its menace. the failure of current treatment strategies is due to emergence of drug resistance in plasmodium falciparum and drug toxicity in human beings. therefore, the development of novel and effective antimalarial drugs is the need of the hour. considering the huge biomedical applications of nan ...201728450172
anaemia following artemisinin-based combination treatments of uncomplicated plasmodium falciparum malaria in children: temporal patterns of haematocrit and the use of uncomplicated hyperparasitaemia as a model for evaluating late-appearing anaemia.in severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (acts) to cause late-appearing anaemia.201728448988
therapeutic efficacy of artemether-lumefantrine against uncomplicated plasmodium falciparum malaria in a high-transmission area in northwest ethiopia.malaria, particularly due to plasmodium falciparum, remains a major public health threat in ethiopia. artemether-lumefantine (al) has been the first-line antimalarial drug against uncomplicated p. falciparum malaria in the country since 2004. regular monitoring of antimalarial drugs is recommended by the world health organization (who) to help early detection of drug resistant strains of the parasite and contain their rapid spread. the objective of this study was to assess the therapeutic effica ...201728445503
the malaria system microapp: a new, mobile device-based tool for malaria diagnosis.malaria is a public health problem that affects remote areas worldwide. climate change has contributed to the problem by allowing for the survival of anopheles in previously uninhabited areas. as such, several groups have made developing news systems for the automated diagnosis of malaria a priority.201728442456
nested multiplex pcr for identification and detection of human plasmodium species including plasmodium knowlesi.to develop a new technique for diagnosis of plasmodium knowlesi and at the same time to be able to discriminate among the diverse species of plasmodium causing human malaria.201728442114
serological measures to assess the efficacy of malaria control programme on ambae island, vanuatu.seroepidemiology can provide evidence for temporal changes in malaria transmission and is an important tool to evaluate the effectiveness of control interventions. during the early 2000s, vanuatu experienced an acute increase in malaria incidence due to a lapse in funding for vector control. after the distribution of subsidised insecticide-treated nets (itns) resumed in 2003, malaria incidence decreased in the subsequent years. this study was conducted to find the serological evidence supporting ...201728441959
chemical constituents and biological activities from branches of colubrina asiatica.sixteen compounds were isolated from a thai medicinal plant, colubrina asiatica. the isolated compounds were elucidated on the basis of spectroscopic methods (ir, 1d and 2d nmr) as six triterpene acids (1-6), five steroids (7-11), one benzoic acid derivative (12), two peptides (13 and 14), one sesquiterpenoid (15) and one jujubogenin (16). compounds 3 and 10 showed antimalarial activity against plasmodium falciparum. compound 5 showed antimycobacterial activity. moreover, compounds 3, 5, 6, 10 a ...201728441887
ferrocenyl and organic novobiocin derivatives: synthesis and their in vitro biological activity.a focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. these compounds were screened for biological activity against a chloroquine-sensitive strain of plasmodium falciparum (3d7) and human breast cancer cell line (hcc38). with the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted i ...201728441548
molecular profile of malaria drug resistance markers of plasmodium falciparum in suriname.in suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in plasmodium falciparum we genotyped the pfk13 propeller domain of p. falciparum in 40 samples as well as other mutations proposed to be associated with artemisinin-resistant mutants. we did not find any mutations previously associated with artemisinin resistance in southeast asia, but we found fixed resistance mutations for chloroquine (cq) and sulfadoxin ...201728438929
malaria profiles and challenges in artemisinin resistance containment in myanmar.this study examined evolving malaria profiles from january, 2010 to december, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in myanmar.201728438194
prevalence of plasmodium falciparum and non-p. falciparum infections in a highland district in ghana, and the influence of hiv and sickle cell disease.in the past two decades, there has been a reported decline in malaria in ghana and the rest of the world; yet it remains the number one cause of mortality and morbidity. human immuno-deficiency virus (hiv) and sickle cell disease (scd) share a common geographical space with malaria in sub-saharan africa and an interaction between these three conditions has been suggested. this study determined the plasmodium falciparum and non-p. falciparum status of symptomatic and non-symptomatic residents of ...201728438159
the malaria testing and treatment landscape in the southern lao people's democratic republic (pdr).in the context of national and regional goals to eliminate malaria by 2030, the center for malaria parasitology and entomology in the lao pdr is implementing strategies to ensure all malaria cases are detected and appropriately treated with first-line artemisinin combination therapy, artemether-lumefantrine (al). timely and relevant evidence to inform policies and strategies is needed to ensure the most effective and efficient use of resources, and to accelerate progress towards elimination goal ...201728438155
antiplasmodial mode of action of pantothenamides: pantothenate kinase serves as a metabolic activator not as a target.n-substituted pantothenamides (panams) are pantothenate analogues with up to nanomolar potency against blood-stage plasmodium falciparum (the most virulent species responsible for malaria). although these compounds are known to target coenzyme a (coa) biosynthesis and/or utilization, their exact mode of action (moa) is still unknown. importantly, panams that retain the natural β-alanine moiety are more potent than other variants, consistent with the involvement of processes that are selective fo ...201728437604
discovery of antimalarial azetidine-2-carbonitriles that inhibit p. falciparum dihydroorotate dehydrogenase.dihydroorotate dehydrogenase (dhodh) is an enzyme necessary for pyrimidine biosynthesis in protozoan parasites of the genus plasmodium, the causative agents of malaria. we recently reported the identification of novel compounds derived from diversity-oriented synthesis with activity in multiple stages of the malaria parasite life cycle. here, we report the optimization of a potent series of antimalarial inhibitors consisting of azetidine-2-carbonitriles, which we had previously shown to target p ...201728435533
watching the availability and use of rapid diagnostic tests (rdts) and artemisinin-based combination therapy (act).at the turn of this new century and after much debate, the malaria community reckoned with failing first line therapies and moved to a global recommendation for deployment of an artemisinin-based combination therapy (act) to treat infections due to plasmodium falciparum. no one said it was going to be easy. this series in the malaria journal reports longitudinal snapshots of how the core pillar of malaria elimination of ensuring universal access to malaria diagnosis and treatment is faring-it is ...201728434397
pre-clinical and clinical development of the first placental malaria vaccine.malaria during pregnancy is a massive health problem in endemic areas. placental malaria infections caused by plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. significant efforts have been invested into preventing the condition. areas covered: pub med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current str ...201728434376
spatial distribution of falciparum malaria infections in zanzibar: implications for focal drug administration strategies targeting asymptomatic parasite carriers.optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. we therefore studied spatial distribution of plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting.201728431115
a no film slot blot for the detection of developing p. falciparum oocysts in mosquitoes.non-microscopy-based assays for sensitive and rapid detection of plasmodium infection in mosquitoes are needed to allow rapid and high throughput measurement of transmission intensity and malaria control program effectiveness. here, we report on a modified enhanced chemiluminescence-based slot blot assay for detection of plasmodium falciparum (pf) circumsporozite protein (pfcsp) expressed on parasite oocysts developing inside the mosquito midgut. this modified assay has several novel features th ...201728430778
identification of tight-binding plasmepsin ii and falcipain 2 inhibitors in aqueous extracts of marine invertebrates by the combination of enzymatic and interaction-based assays.natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. however, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. in the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous ex ...201728430158
comparison of methods for detecting asymptomatic malaria infections in the china-myanmar border area.sensitive methods for detecting asymptomatic malaria infections are essential for identifying potential transmission reservoirs and obtaining an accurate assessment of malaria epidemiology in low-endemicity areas aiming to eliminate malaria. pcr techniques to detect parasite nucleic acids (dna or rna) are among the most commonly used molecular methods. however, most of these methods are of low throughput and cannot be used for large-scale molecular epidemiological studies. a recently developed c ...201728427455
household level spatio-temporal analysis of plasmodium falciparum and plasmodium vivax malaria in ethiopia.the global decline of malaria burden and goals for elimination has led to an increased interest in the fine-scale epidemiology of malaria. micro-geographic heterogeneity of malaria infection could have implications for designing targeted small-area interventions.201728427451
efficacies of dha-ppq and as/sp in patients with uncomplicated plasmodium falciparum malaria in an area of an unstable seasonal transmission in sudan.artemisinin-based combination therapy (act), together with other control measures, have reduced the burden of falciparum malaria in sub-saharan countries, including sudan. sudan adopted act in 2004 with a remarkable reduction in mortality due to falciparum malaria. however, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (as/sp) has created new challenges to the control of malaria in sudan. a search for an alternative drug of choice for treating uncom ...201728427409
association between fcγ receptor iia, iiia and iiib genetic polymorphisms and susceptibility to severe malaria anemia in children in western kenya.naturally-acquired immunity to plasmodium falciparum malaria develops after several episodes of infection. fc gamma receptors (fcγrs) bind to immunoglobulin g (igg) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. fcγr polymorphisms influence binding affinity to iggs and consequently, can influence clinical malaria outcomes. specifically, variations in fcγriia -131arg/his, fcγriiia-176f/v and fcγriiib-na1/na2 modulate immune responses thr ...201728427365
cd4 t-cell expression of ifn-γ and il-17 in pediatric malarial anemia.in plasmodium falciparum holoendemic transmission regions of western kenya, life-threatening pediatric malaria manifests primarily as severe malarial anemia (sma, hb≤6.0 g/dl with any density parasitemia). to determine the role that cd4+ t-cell-driven inflammatory responses have in the pathogenesis of sma, peripheral cd4+ t-cell populations and their intracellular production of pro-inflammatory cytokines (ifn-γ and il-17) were characterized in children aged 12-36 months of age stratified into tw ...201728426727
extensive alterations of blood metabolites in pediatric cerebral malaria.cerebral malaria (cm) presents as an encephalopathy and is due to infection with plasmodium falciparum. patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. the etiology of the coma and seizures are poorly understood. circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. we carried out a comprehensive an ...201728426698
plasmodium falciparum otu-like cysteine protease (pfotu) is essential for apicoplast homeostasis and associates with noncanonical role of atg8.the metabolic pathways associated with the mitochondrion and the apicoplast in plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. in the present study, we have identified functional role of a novel ovarian tumour unit (otu) domain-containing cysteine protease of plasmodium falciparum (pfotu). a c-terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. detailed studies showed ...201728423214
genetic and epigenetic changes in host abcb1 influences malaria susceptibility to plasmodium falciparum.multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to anti-malarial drugs in the population. abcb1 is one of the well-studied membrane transporter genes that code for the p-glycoprotein (an efflux protein) and whose effect on malaria disease predisposition and susceptibility to drugs remains to be understood. we studied the association of single nucleotide variations in human abcb1 that influences its function i ...201728422980
enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine.the leading malaria vaccine in development is the circumsporozoite protein (csp)-based particle vaccine, rts,s, which targets the pre-erythrocytic stage of plasmodium falciparum infection. it induces modest levels of protective efficacy, thought to be mediated primarily by csp-specific antibodies. we aimed to enhance vaccine efficacy by generating a more immunogenic csp-based particle vaccine and therefore developed a next-generation rts,s-like vaccine, called r21. the major improvement is that ...201728422178
metal-dna interactions improve signal in high-resolution melting of dna for species differentiation of plasmodium parasite.the success of high-resolution melting (hrm) analysis for distinguishing similar dnas with minor base mismatch differences is limited. here, metal-mediated structural change in dna has been exploited to amplify hrm signals leading to differentiation of target dnas in an orthologous gene corresponding to four plasmodium species. conserved 26-mer ssdnas from ldh gene of the four plasmodium species were employed as targets. a capture probe (cp) that is fully complementary to the plasmodium falcipar ...201728421327
high resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic plasmodium populations.emergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specific and field-deployable molecular tools for detection and surveillance of validated drug resistance markers. such tools would allow early detection of mutations in resistance loci. the aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with different levels of malaria endemicity and histor ...201728420422
molecular surveillance of plasmodium falciparum drug resistance in the republic of congo: four and nine years after the introduction of artemisinin-based combination therapy.resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. following the global spread of chloroquine-resistant parasites, the republic of congo adopted artemisinin-based combination therapy (act) in 2006 as a first-line treatment for uncomplicated malaria. to assess the impacts after implementation of act, a molecular surveillance for anti-malarial drug resistance was conducted in congo 4 and 9 years after the introduction of act.201728420403
distinct parasite populations infect individuals identified through passive and active case detection in a region of declining malaria transmission in southern zambia.substantial reductions in the burden of malaria have been documented in parts of sub-saharan africa, with elimination strategies and goals being formulated in some regions. within this context, understanding the epidemiology of low-level malaria transmission is crucial to achieving and sustaining elimination. a 24 single-nucleotide-polymorphism plasmodium falciparum molecular barcode was used to characterize parasite populations from infected individuals identified through passive and active cas ...201728420399
assessment of copy number variation in genes related to drug resistance in plasmodium vivax and plasmodium falciparum isolates from the brazilian amazon and a systematic review of the literature.parasite resistance to anti-malarials represents a great obstacle for malaria elimination. the majority of studies have investigated the association between single-nucleotide polymorphisms (snps) and drug resistance; however, it is becoming clear that the copy number variation (cnv) is also associated with this parasite phenotype. to provide a baseline for molecular surveillance of anti-malarial drug resistance in the brazilian amazon, the present study characterized the genetic profile of both ...201728420389
synthesis and evaluation of anti-plasmodial and cytotoxic activities of epoxyazadiradione derivatives.epoxyazadiradione (1), a major compound derived from neem oil, showed modest anti-plasmodial activity against cq-resistant and cq-sensitive strains of the most virulent human malaria parasite p. falciparum. a series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against cq-sensitive (ic50 2.8 ± 0.29 μm and 1.5 ± 0.01 μm) and ...201728419927
expression of the plasmodium falciparum clonally variant clag3 genes in human infections.many genes of the malaria parasite plasmodium falciparum show clonally variant expression regulated at the epigenetic level. these genes participate in fundamental host-parasite interactions and contribute to adaptive processes. however, little is known about their expression patterns during human infections. a peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds.201728419281
[role of primaquine in malaria control and elimination in french-speaking africa].primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug in french-speaking african countries. it acts against the liver stage parasites of all human malaria species, asexual blood stages of plasmodium vivax and, to a lesser degree, plasmodium falciparum; p. falciparum mature gametocytes, and p. vivax and plasmodium ovale hypnozoites. gastrointestinal disturbances are its most common side effects. the clinical utility of primaquine is limited due to its hematological side ...201728417346
capturing in vivo rna transcriptional dynamics from the malaria parasite plasmodium falciparum.to capture the transcriptional dynamics within proliferating cells, methods to differentiate nascent transcription from preexisting mrnas are desired. one approach is to label newly synthesized mrna transcripts in vivo through the incorporation of modified pyrimidines. however, the human malaria parasite, plasmodium falciparum, is incapable of pyrimidine salvage for mrna biogenesis. to capture cellular mrna dynamics during plasmodium development, we engineered parasites that can salvage pyrimidi ...201728416533
travel and the emergence of high-level drug resistance in plasmodium falciparum in southwest uganda: results from a population-based study.the i164l mutation on the dhfr gene confers high level resistance to sulfadoxine-pyrimethamine (sp) but it is rare in africa except in a cluster of reports where prevalence >10% in highland areas of southwest uganda and eastern rwanda. the occurrence of the dhfr i164l mutation was investigated in community surveys in this area and examined the relationship to migration.201728415996
epigenetic landscapes underlining global patterns of gene expression in the human malaria parasite, plasmodium falciparum.the dynamic chromatin landscape displaying combinatorial complexity of the epigenome impacts gene expression that underlies many events of differentiation and cell cycle progression. in the past few years, epigenetic mechanisms have emerged as important processes involved in the tight gene regulation in malaria parasites, plasmodium spp. focusing predominantly on plasmodium falciparum, the species associated with the most severe form of the disease, many advances have been made in our understand ...201728414071
an intricate case of multidrug resistant plasmodium falciparum isolate imported from cambodia.imported cases of multidrug resistant plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in western countries and their management is often challenging. this is also due to an inadequate knowledge and implementation of health prevention measures.201728410610
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