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comprehensive review on various strategies for antimalarial drug discovery.the resistance of malaria parasites to existing drugs carries on growing and progressively limiting our ability to manage this severe disease and finally lead to a massive global health burden. till now, malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. very few new antimalarials were developed in the past 50 years. among recent approaches, identification of novel chemotherapeutic targets, exploration of natural products with medicinal significance, ...201727886547
activation and clustering of a plasmodium falciparum var gene are affected by subtelomeric sequences.the plasmodium falciparum var multigene family encodes the cytoadhesive, variant antigen pfemp1. p. falciparum antigenic variation and cytoadhesion specificity are controlled by epigenetic switching between the single, or few, simultaneously expressed var genes. most var genes are maintained in perinuclear clusters of heterochromatic telomeres. the active var gene(s) occupy a single, perinuclear var expression site. it is unresolved whether the var expression site forms in situ at a telomeric cl ...201727860263
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
an opsonic phagocytosis assay for plasmodium falciparum sporozoites.plasmodium falciparum malaria remains the deadliest parasitic disease worldwide. vaccines targeting the preerythrocytic sporozoite and liver stages have the potential to entirely prevent blood-stage infection and disease, as well as onward transmission. sporozoite surface and secreted proteins are leading candidates for inclusion in a preerythrocytic stage-specific, antibody-based vaccine. preclinical functional assays to identify humoral correlates of protection in vitro and to validate novel s ...201727881488
de novo lead optimization of triazine derivatives identifies potent antimalarials.malaria is a life-threatening disease caused by plasmodium parasites among which plasmodium falciparum is the most deadly. due to the widespread resistance of the current antimalarial drugs, intense research efforts are focused on identification of new and potent antimalarials. we report here, a structure based drug discovery strategy for design of a series of effective and novel triazine based antimalarials. the x-ray structure of p. falciparum methyl transferase (pfpmt) is used as a target as ...201727880887
steroid pulse therapy may mitigate prolonged neurological manifestations after eradication of severe plasmodium falciparum parasitemia.a 58-year-old japanese man with a high parasitemia of plasmodium falciparum, returning from uganda, was admitted to our hospital since his consciousness level rapidly deteriorated after the initial dose of mefloquine. despite the parasitemia was cleared by quinine by day 7, the coma remained unchanged and diffuse leukoencephalopathy was detected on magnetic resonance image. steroid pulse therapy was initiated on day 8. subsequently, the neurological manifestations improved and he was discharged ...201727853090
multicenter pivotal clinical trial of urine malaria test for rapid diagnosis of plasmodium falciparum malaria.the need to expand malaria diagnosis capabilities alongside policy requirements for mandatory testing before treatment motivates exploration of noninvasive rapid diagnostic tests (rdts). we report the outcome of the first cross-sectional, single-blind clinical performance evaluation of a urine malaria test (umt) for diagnosis of plasmodium falciparum malaria in febrile patients. matched urine and finger-prick blood samples from participants ≥2 years of age with fever (axillary temperature of ≥37 ...201727847373
computational analysis, structural modeling and ligand binding site prediction of plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate synthase.malaria remains one of the most serious infectious diseases in the world. there are five human species of the plasmodium genus, of which plasmodium falciparum is the most virulent and responsible for the vast majority of malaria related deaths. the unique biochemical processes that exist in plasmodium falciparum provide a useful way to develop novel inhibitors. one such biochemical pathway is the methyl erythritol phosphate pathway (mep), required to synthesize isoprenoid precursors. in the pres ...201727842226
efficacy and safety of re-treatment with the same artemisinin-based combination treatment (act) compared with an alternative act and quinine plus clindamycin after failure of first-line recommended act (quinact): a bicentre, open-label, phase 3, randomised controlled trial.quinine or alternative artemisinin-based combination treatment (act) is the recommended rescue treatment for uncomplicated malaria. however, patients are often re-treated with the same act though it is unclear whether this is the most suitable approach. we assessed the efficacy and safety of re-treating malaria patients with uncomplicated failures with the same act used for the primary episode, compared with other rescue treatments.201727840069
estimation of the in vivo mic of cipargamin in uncomplicated plasmodium falciparum malaria.the mic of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. to ensure the cure of malaria, the mic must be exceeded until all parasites have been eliminated. the development of highly sensitive and accurate pcr quantitation of low-density malaria parasitemia enables the prospective pharmacokinetic-pharmacodynamic (pk-pd) characterization of antimalarial drug effects and now allows identification of the ...201727872070
recurrence of plasmodium falciparum after treatment with quinine and doxycycline in the amazon basin.to investigate whether the recurrence of infection by plasmodium falciparum in patients from the brazilian amazon was caused by an inadequate exposure to quinine.201727862676
in vitro sensitivity of antimalarial drugs and correlation with clinico-parasitological response following treatment with a 3-day artesunate-mefloquine combination in patients with falciparum malaria along the thai-myanmar border.a 3-day artesunate-mefloquine combination therapy has been using as first-line treatment for acute uncomplicated plasmodium falciparum malaria in thailand since 1995 on the background of mefloquine resistance. the aim of the present study was to assess sensitivity of p. falciparum isolates (n=44) in an area along the thai-myanmar border (year 2009) to artesunate, mefloquine, chloroquine and quinine, including their correlation with clinico-parasitological response. twenty, 19, and 5 isolates wer ...201727866919
rarity of mixed species malaria with plasmodium falciparum and plasmodium malariae in travelers to saarland in germany.malaria is an acute, life-threatening infectious disease that spreads in tropical and subtropical regions. malaria is mainly brought over to germany by travelers, so the disease can be overlooked due to its nonspecific symptoms and a lack of experience of attending physicians. the aim of this study was to analyze, retrospectively, epidemiological and clinical data from patients examined for malaria. patient data were collected from hospital charts at the department of internal medicine, saarland ...201727826886
dissecting malaria biology and epidemiology using population genetics and genomics.molecular approaches have an increasingly recognized utility in surveillance of malaria parasite populations, not only in defining prevalence and incidence with higher sensitivity than traditional methods, but also in monitoring local and regional parasite transmission patterns. in this review, we provide an overview of population genetic and genomic studies of human-infecting plasmodium species, highlighting recent advances in the field. in accordance with the renewed impetus for malaria eradic ...201727825828
differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance.antibodies play a key role in acquired human immunity to plasmodium falciparum (pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. we hypothesized that there would be differences in the rate of acquisition of ant ...201727837017
biology of malaria transmission.understanding transmission biology at an individual level is a key component of intervention strategies that target the spread of malaria parasites from human to mosquito. gametocytes are specialized sexual stages of the malaria parasite life cycle developed during evolution to achieve crucial steps in transmission. as sexual differentiation and transmission are tightly linked, a deeper understanding of molecular and cellular events defining this relationship is essential to combat malaria. rece ...201727836912
successful engraftment of human hepatocytes in upa-scid and frg(®) ko mice.mice with humanized chimeric liver are promising in vivo tools to evaluate the efficacy of novel compounds or vaccine induced antibodies directed against pathogens that infect the human liver. in addition they can be used to study the human-type metabolism of medicinal compounds and hepatotoxicity.201727830549
phenotypic screens identify parasite genetic factors associated with malarial fever response in plasmodium falciparum piggybac mutants.malaria remains one of the most devastating parasitic diseases worldwide, with 90% of the malaria deaths in africa in 2013 attributable to plasmodium falciparum. the clinical symptoms of malaria include cycles of fever, corresponding to parasite rupture from red blood cells every 48 h. parasite pathways involved in the parasite's ability to survive the host fever response, and indeed, the functions of ~40% of p. falciparum genes as a whole, are still largely unknown. here, we evaluated the poten ...201727830190
molecular expression of aquaporin mrnas in the northern house mosquito, culex pipiens.aquaporins (aqps) are a family of membrane-bound proteins, originally described as water-channels, that broadly exist in prokaryotic and eukaryotic cells. however, some aqps can transport small molecules (e.g. urea, glycerol) along with or preferentially to water. previous work in the mosquitoes aedes aegypti and anopheles gambiae have characterized the molecular expression of one or more aqp genes and shown that they are involved in water homeostasis after blood feeding, tolerance to dehydratio ...201727773635
enzyme-free electrochemical immunosensor based on methylene blue and the electro-oxidation of hydrazine on pt nanoparticles.enzyme-free electrochemical sensors enable rapid, high sensitivity measurements without the limitations associated with enzyme reporters. however, the performance of non-enzymatic electrochemical sensors tends to suffer from slow electrode kinetics and poor signal stability. we report a new enzyme-free electrochemical immunosensor based on a unique competitive detection scheme using methylene blue (mb), hydrazine and platinum nanoparticles (pt nps). this scheme is coupled with a robust immunosan ...201727829560
genetic markers associated with dihydroartemisinin-piperaquine failure in plasmodium falciparum malaria in cambodia: a genotype-phenotype association study.as the prevalence of artemisinin-resistant plasmodium falciparum malaria increases in the greater mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast asia and beyond.201727818095
simple detection of single nucleotide polymorphism in plasmodium falciparum by snp-lamp assay combined with lateral flow dipstick.the significant strides made in reducing global malaria burden over the past decades are being threatened by the emergence of multi-drug resistant malaria. mechanisms of resistance to several classes of antimalarial drugs have been linked to key mutations in the plasmodium falciparum genes. pyrimethamine targets the dihydrofolate reductase of the bifunctional dihydrofolate reductase thymidylate synthase (dhfr-ts), and specific point mutations in the dhfr-ts gene have been assigned to resistant p ...201727816495
synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies.novel series of naphthyl bearing 1,2,3-triazoles (4a-t) were synthesized and evaluated for their in vitro antiplasmodial activity against pyrimethamine (pyr)-sensitive and resistant strains of plasmodium falciparum. the synthesized compounds were assessed for their cytotoxicity employing human embryonic kidney cell line (hek-293), and none of them was found to be toxic. among them 4j, 4k, 4l, 4m, 4n, 4t exhibited significant antiplasmodial activity in both strains, of which compounds 4m, 4n and ...201727816268
caged garcinia xanthones, a novel chemical scaffold with potent antimalarial activity.caged garcinia xanthones (cgxs) constitute a family of natural products that are produced by tropical/subtropical trees of the genus garcinia cgxs have a unique chemical architecture, defined by the presence of a caged scaffold at the c ring of a xanthone moiety, and exhibit a broad range of biological activities. here we show that synthetic cgxs exhibit antimalarial activity against plasmodium falciparum, the causative parasite of human malaria, at the intraerythrocytic stages. their activity c ...201727799215
new genetic marker for piperaquine resistance in plasmodium falciparum. 201727818096
critical evaluation of molecular monitoring in malaria drug efficacy trials and pitfalls of length-polymorphic markers.estimation of drug efficacy in antimalarial drug trials requires parasite genotyping to distinguish new infections from treatment failures. when using length-polymorphic molecular markers, preferential amplification of short fragments can compromise detection of coinfections, potentially leading to misclassification of treatment outcome. we quantified minority clone detectability and competition among msp1, msp2, and glurp amplicons using mixtures of plasmodium falciparum strains and investigate ...201727821442
a surrogate marker of piperaquine-resistant plasmodium falciparum malaria: a phenotype-genotype association study.western cambodia is the epicentre of plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. genetic tools to detect the multidrug-resistant parasites are needed. artemisinin resistance can be tracked using the k13 molecular marker, but no marker exists for piperaquine resistance. we aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures.201727818097
altered plasmodium falciparum sensitivity to the antiretroviral protease inhibitor lopinavir associated with polymorphisms in pfmdr1.the hiv protease inhibitor lopinavir inhibits plasmodium falciparum aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. resistance to lopinavir was selected in vitro over ∼9 months, with ∼4-fold decreased sensitivity. whole-genome sequencing of resistant parasites showed a mutation and increased copy number in pfmdr1 and a mutation in a protein of unknown fu ...201727821443
plasmodium falciparum genetic diversity in continental equatorial guinea before and after introduction of artemisinin-based combination therapy.efforts to control malaria may affect malaria parasite genetic variability and drug resistance, the latter of which is associated with genetic events that promote mechanisms to escape drug action. the worldwide spread of drug resistance has been a major obstacle to controlling plasmodium falciparum malaria, and thus the study of the origin and spread of associated mutations may provide some insights into the prevention of its emergence. this study reports an analysis of p. falciparum genetic div ...201727795385
shining new light on ancient drugs: preparation and subcellular localisation of novel fluorescent analogues of cinchona alkaloids in intraerythrocytic plasmodium falciparum.fluorescent derivatives of the archetypal antimalarial quinine and its diastereomer, quinidine, suitable for cellular imaging have been synthesised by attaching the small extrinsic fluorophore, nbd. interactions of these derivatives with ferriprotoporphyrin ix were evaluated to verify that insights generated by live-cell imaging were relevant to the parent molecules. these analogues are shown by confocal and super-resolution microscopy to accumulate selectively in plasmodium falciparum. localisa ...201727785512
mathematical modelling to guide drug development for malaria elimination.mathematical models of the dynamics of a drug within the host are now frequently used to guide drug development. these generally focus on assessing the efficacy and duration of response to guide patient therapy. increasingly, antimalarial drugs are used at the population level, to clear infections, provide chemoprevention, and to reduce onward transmission of infection. however, there is less clarity on the extent to which different drug properties are important for these different uses. in addi ...201727727128
preferential expression of domain cassettes 4, 8 and 13 of plasmodium falciparum erythrocyte membrane protein 1 in severe malaria imported in france.severe plasmodium falciparum malaria (sm) involves cytoadhesion of parasitized red blood cells, mediated by p. falciparum erythrocyte membrane protein 1, which is encoded by var genes. expression of var gene group a and b or encoding domain cassettes dc4, dc5, dc8 and dc13 has been implicated in sm in african children, but no data exist in the context of imported malaria. the aim of this study was to investigate var gene expression linked to clinical presentation and host factors in sm imported ...201727773760
receptor for activated c-kinase 1 (pfrack1) is required for plasmodium falciparum intra-erythrocytic proliferation.emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of plasmodium falciparum proliferation, thus allowing identification of new drug targets. the well-conserved protein receptor for activated c-kinase 1 (rack1) was originally identified in mammalian cells as an anchoring protein for protein kinase c (pkc) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. t ...201727732881
plasmodium falciparum isolates from patients with uncomplicated malaria promote endothelial inflammation.the ability of plasmodium falciparum infected erythrocytes (pf-ies) to activate endothelial cells has been described; however, the interaction of the endothelium with pf-ies field isolates from patients has been less characterized. previous reports have shown that isolates alter the endothelial permeability and apoptosis. in this study, the adhesion of 19 uncomplicated malaria isolates to human dermal microvascular endothelial cells (hdmec), and their effect on the expression of icam-1 and proin ...201727717894
malaria deaths in usa and europe: "it's the same old story". it is time for a change. 201727524681
late manifestation of a mixed plasmodium falciparum and plasmodium malariae infection in a non-immune toddler after traveling to chad. 201727238908
might interspecific interactions between pathogens drive host evolution? the case of plasmodium species and duffy-negativity in human populations.malarial infections have long been recognized as a driver of human evolution, as demonstrated by the influence of plasmodium falciparum on sickle-cell anemia persistence. duffy-negativity is another blood disorder thought to have been selected because it confers nearly complete resistance against plasmodium vivax infection. recent evidence suggests that the benefits of being duffy-negative cannot be expected to play a strong selective pressure on humans, whereas its costs cannot be considered as ...201727765439
the production and antiprotozoal activity of abietane diterpenes in salvia austriaca hairy roots grown in shake flasks and bioreactor.the biomass and concentration of bioactive quinone methide-type diterpenes in hairy roots of salvia austriaca were determined and compared with levels of these metabolites in roots of field-grown plants. the cultures were maintained in shake flasks and a nutrient sprinkle bioreactor. diterpene production was more efficient in the shake flask root culture than the bioreactor one. biomass and diterpene production within the shake flask culture was evaluated using schenk and hildebrandt (sh), gambo ...201727070932
biochemical and structural characterization of selective allosteric inhibitors of the plasmodium falciparum drug target, prolyl-trna-synthetase.plasmodium falciparum (pf) prolyl-trna synthetase (prors) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. in this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit pfprors enzyme activity versus homo sapiens (hs) prors. x-ray crystallography structures were solved for apo, as well as substrate- and inhibitor-bound forms of pfprors. we identified two new inhibitors ...201727798837
far from the madding crowd: the molecular basis for immunological escape of plasmodium falciparum.like thomas hardy's famous novel far from the madding crowd, plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. the 3d structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as ...201727698284
evaluation of 7-arylaminopyrazolo[1,5-a]pyrimidines as anti-plasmodium falciparum, antimalarial, and pf-dihydroorotate dehydrogenase inhibitors.malaria remains one of the most serious global infectious diseases. an important target for antimalarial chemotherapy is the enzyme dihydroorotate dehydrogenase from plasmodium falciparum (pfdhodh), which is responsible for the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthetic pathway. in this study, we have designed and synthesized fifteen 7-arylpyrazolo[1,5-a]pyrimidine derivatives using ring bioisosteric replacement and molecular hybridization of functional groups ...201727744189
backbone and side-chain resonance assignments of plasmodium falciparum sumo.one of the most debilitating diseases malaria, in its different forms, is caused by protozoan of plasmodium species. deadliest among these forms is the "cerebral malaria" which is afflicted upon by plasmodium falciparum. plasmodium adopts numerous strategies including various post-translational modifications (ptms) to infect and survive in the human host. these ptms have proven their critical requirement in the plasmodium biology. recently, sumoylation has been characterized as one of the import ...201727699617
binding and inhibition of spermidine synthase from plasmodium falciparum and implications for in vitro inhibitor testing.the aminopropyltransferase spermidine synthase (spds) is a promising drug target in cancer and in protozoan diseases including malaria. plasmodium falciparum spds (pfspds) transfers the aminopropyl group of decarboxylated s-adenosylmethionine (dcadomet) to putrescine or to spermidine to form spermidine or spermine, respectively. in an effort to understand why efficient inhibitors of pfspds have been elusive, the present study uses enzyme activity assays and isothermal titration calorimetry with ...201727661085
role of an. culicifacies as a vector of malaria in changing ecological scenario of northeastern states of india.malaria has become endemic and subject of concern in most part of the india especially northeastern states of india. surveys before 2000 revealed that anopheles minimus was major vector responsible for transmission of malaria in this region followed by an. dirus and an. fluviatilis. however, recent studies indicate replacement of an. minimus vector by an. culicifacies due to different ecological changes and change in landuse pattern etc. the objective of present study was to explore the vectoria ...201727681550
impact of insecticide-treated bednet use on malaria prevalence in benishangul-gumuz regional state, ethiopia.in ethiopia, nearly 10 million insecticide-treated bednets (itns) were distributed between 2004 and 2005; which touched 56 million in 2012. the study was aimed to determine the impact of these bednets on malaria prevalence, in yaso district of benishangul-gumuz region, western ethiopia.201727681544
seasonal malaria chemoprevention with sulphadoxine-pyrimethamine and amodiaquine selects pfdhfr-dhps quintuple mutant genotype in mali.seasonal malaria chemoprevention (smc) with sulphadoxine-pyrimethamine (sp) plus amodiaquine (aq) is being scaled up in sahelian countries of west africa. however, the potential development of plasmodium falciparum resistance to the respective component drugs is a major concern.201727662368
malaria in travellers returning or migrating to canada: surveillance report from cantravnet surveillance data, 2004-2014.malaria remains the most common specific cause of fever in returned travellers and can be life-threatening. we examined demographic and travel correlates of malaria among canadian travellers and immigrants to identify groups for targeted pretravel intervention.201727730099
the role of haematological parameters in predicting malaria with special emphasis on neutrophil lymphocyte count ratio and monocyte lymphocyte ratio: a single institutional experience.malaria is a mosquito borne disease which is a major public health problem and a leading cause of morbidity and mortality worldwide. various haematological parameters have been studied to help predict malaria, such as alteration in the leucocyte count, platelet counts and erythrocyte counts. the neutrophil lymphocyte count ratio (nlcr) was found to have a good predictive value in systemic inflammation, particularly in critical care setting.201727722104
comparison of protein expression pattern between the plasmodium falciparum chloroquine-resistant rkl9 and chloroquine-sensitive mrc2 strains.the objective of this study was to compare the protein expression patterns of plasmodium falciparum extracellular and intracellular proteins separated by two-dimensional electrophoresis (2-de) from the chloroquine-sensitive (cqs) mrc2 strain and chloroquine-resistant (cqr) rkl9 strain. materials and methods: both the extracellular protein (ecp) and intracellular protein (icp) were extracted and solubilized. the proteins were separated by 2-de, first based on their charges using isoelectric focus ...201727722102
hyperparasitaemia and phagocytosis of plasmodium falciparum in fatal cerebral malaria. 201727681555
severe malaria: what's new on the pathogenesis front?plasmodium falciparum causes the most severe and fatal form of malaria in humans with over half a million deaths each year. cerebral malaria, a complex neurological syndrome of severe falciparum malaria, is often fatal and represents a major public health burden. despite vigorous efforts, the pathophysiology of cerebral malaria remains to be elucidated, thereby hindering the development of adjunctive therapies. in recent years, multidisciplinary and collaborative approaches have led to groundbre ...201727670365
4-aminoquinoline-ferrocenyl-chalcone conjugates: synthesis and anti-plasmodial evaluation.a series of aliphatic and aromatic substituted 1h-1,2,3-triazole-tethered 4-amino-quinoline-ferrocenylchalcone conjugates has been synthesized and evaluated for anti-plasmodial activity. the conjugates with flexible aliphatic (aminoethanol or aminopropanol) substituents on the quinoline ring showed better anti-plasmodial activities compared to those with cyclic (piperazine or aminophenol) substituents. the conjugate 17j was the most potent and non-cytotoxic, with an ic50 value of 0.37 μm against ...201727688182
discovery of new hit-molecules targeting plasmodium falciparum through a global sar study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold.from 4 antiplasmodial hit-molecules identified in 2-trichloromethylquinazoline series, we conducted a global structure-activity relationship (sar) study involving 26 compounds and covering 5 molecular regions (i - v), aiming at defining the corresponding pharmacophore and identifying new bioactive derivatives. thus, after studying the aniline moiety in detail, thienopyrimidine, quinoline and quinoxaline bio-isosters were synthesized and tested on the k1 multi-resistant p. falciparum strain, alon ...201727654395
atpase activity of plasmodium falciparum mlh is inhibited by dna-interacting ligands and dsrnas of mlh along with uvrd curtail malaria parasite growth.malaria caused by plasmodium falciparum is the major disease burden all over the world. recently, the situation has deteriorated because the malarial parasites are becoming progressively more resistant to numerous commonly used antimalarial drugs. thus, there is a critical requirement to find other means to restrict and eliminate malaria. the mismatch repair (mmr) machinery of parasite is quite unique in several ways, and it can be exploited for finding new drug targets. mutl homolog (mlh) is on ...201727624787
the clinical impact of artemisinin resistance in southeast asia and the potential for future spread.artemisinins are the most rapidly acting of currently available antimalarial drugs. artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (acts) are the foundation of modern falciparum malaria treatment globally. their safety and tolerability profile is excellent. unfortunately, plasmodium falciparum infections with mutations in the 'k13' gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients t ...201727613271
in silico identification of promiscuous scaffolds as potential inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase for treatment of falciparum malaria.malaria remains one of the prevalent infectious diseases worldwide. plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate reductoisomerase (pfdxr) plays a role in isoprenoid biosynthesis in the malaria parasite, making this parasite enzyme an attractive target for antimalarial drug design. fosmidomycin is a promising dxr inhibitor, which showed safety as well as efficacy against plasmodium falciparum malaria in clinical trials. however, due to its poor oral bioavailability and non-drug-like prope ...201727650666
spontaneous subdural empyema following a high-parasitemia falciparum infection in a 58-year-old female from a malaria-endemic region: a case report.malaria remains a significant public health problem of the tropical world. falciparum malaria is most prevalent in the sub-saharan african region, which harbors about 90% of all malaria cases and fatalities globally. infection by the falciparum species often manifests with a spectrum of multi-organ complications (eg, cerebral malaria), some of which are life-threatening. spontaneous subdural empyema is a very rare complication of cerebral malaria that portends a very poor prognosis unless diagno ...201727635411
correction: hemoglobin e prevalence among ethnic groups residing in malaria-endemic areas of northern thailand and its lack of association with plasmodium falciparum invasion in vitro.[this corrects the article doi: 10.1371/journal.pone.0148079.].201727631391
the effectiveness of natural diarylheptanoids against trypanosoma cruzi: cytotoxicity, ultrastructural alterations and molecular modeling studies.curcumin (cur) is the major constituent of the rhizomes of curcuma longa and has been widely investigated for its chemotherapeutic properties. the well-known activity of cur against leishmania sp., trypanosoma brucei and plasmodium falciparum led us to investigate its activity against trypanosoma cruzi. in this work, we tested the cytotoxic effects of cur and other natural curcuminoids on different forms of t. cruzi, as well as the ultrastructural changes induced in epimastigote form of the para ...201727658305
correction: targeting of a transporter to the outer apicoplast membrane in the human malaria parasite plasmodium falciparum.[this corrects the article doi: 10.1371/journal.pone.0159603.].201727548067
a case of falciparum malaria: acute hearing loss as the initial symptom.a 49-year-old healthy woman, who returned from burkina faso, visited an ear, nose, and throat clinic with complaints of left hearing loss, tinnitus, and dizziness. pure tone audiometry demonstrated bilateral mild sensorineural hearing loss. three days later, she was transported in an ambulance to a general hospital due to high fever and disturbance of consciousness. plasmodium falciparum was found in the peripheral blood smear. after diagnosing severe falciparum malaria with cerebral involvement ...201727578030
recent insights into humoral immunity targeting plasmodium falciparum and plasmodium vivax malaria.recent efforts in malaria control have led to marked reductions in malaria incidence. however, new strategies are needed to sustain malaria elimination and eradication and achieve the world health organization goal of a malaria-free world. the development of highly effective vaccines would contribute to this goal and would be facilitated by a comprehensive understanding of humoral immune responses targeting plasmodium falciparum and plasmodium vivax malaria. new tools are required to facilitate ...201727451359
differential time-dependent volumetric and surface area changes and delayed induction of new permeation pathways in p. falciparum-infected hemoglobinopathic erythrocytes.during intraerythrocytic development, plasmodium falciparum increases the ion permeability of the erythrocyte plasma membrane to an extent that jeopardizes the osmotic stability of the host cell. a previously formulated numeric model has suggested that the parasite prevents premature rupture of the host cell by consuming hemoglobin (hb) in excess of its own anabolic needs. here, we have tested the colloid-osmotic model on the grounds of time-resolved experimental measurements on cell surface are ...201727450804
toward "homolactic" fermentation of glucose and xylose by engineered saccharomyces cerevisiae harboring a kinetically efficient l-lactate dehydrogenase within pdc1-pdc5 deletion background.l-lactic acid is an important platform chemical and its production from the lignocellulosic sugars glucose and xylose is, therefore, of high interest. tolerance to low ph and a generally high robustness make saccharomyces cerevisiae a promising host for l-lactic acid fermentation but strain development for effective utilization of both sugars is an unsolved problem. the herein used s. cerevisiae strain ibb10b05 incorporates a nadh-dependent pathway for oxidoreductive xylose assimilation within c ...201727426989
distinct genomic architecture of plasmodium falciparum populations from south asia.previous whole genome comparisons of plasmodium falciparum populations have not included collections from the indian subcontinent, even though two million indians contract malaria and about 50,000 die from the disease every year. stratification of global parasites has revealed spatial relatedness of parasite genotypes on different continents. here, genomic analysis was further improved to obtain country-level resolution by removing var genes and intergenic regions from distance calculations. p. ...201727457272
an evolutionary conserved zinc finger protein is involved in toxoplasma gondii mrna nuclear export.apicomplexan parasites are responsible for some of the most deadly parasitic diseases affecting humans and livestock. there is an urgent need for new medicines that will target apicomplexan-specific pathways. we characterized a toxoplasma gondii c2h2 zinc finger protein, named tgznf2, which is conserved among eukaryotes. we constructed an inducible ko strain (iko-tgznf2) for this gene where the tgznf2 gene expression is repressed in the presence of a tetracycline analog (atc). we showed that the ...201727385072
historical review: does falciparum malaria destroy isolated tribal populations?many isolated populations of tribal peoples were nearly destroyed when they first contacted infectious diseases particularly respiratory pathogens such as measles and smallpox. surviving groups have often been found to have declining populations in the face of multiple social and infectious threats. malaria, especially plasmodium falciparum, was thought to be a major cause of depopulation in some tribal peoples isolated in tropical jungles. the dynamics of such host parasite interactions is uncl ...201727555283
active v. passive surveillance for malaria in remote tribal belt of central india: implications for malaria elimination.balaghat district in central india is characterized by perennial malaria transmission. in this study, we have estimated malaria parasite rates by microscopic examination of blood smears by conducting active (acd) and passive surveillance (pcd) in the villages of baihar community health center (chc) during january 2012-december 2012. comparison of the results of two methods revealed that acd (active case detection) in villages provides relatively large numbers of malaria positive cases (1408/3601 ...201727585412
imaging flow cytometry for the screening of compounds that disrupt the plasmodium falciparum digestive vacuole.malaria, despite being one of the world's oldest infectious diseases, remains difficult to eradicate because the parasite is rapidly developing resistance to frontline chemotherapies. previous studies have shown that the parasite exhibits features resembling programmed cell death upon treatment with drugs that disrupt its digestive vacuole (dv), providing a phenotypic readout that can be detected using the imaging flow cytometer. large compound collections can thus be screened to identify drugs ...201727389304
no reduction in hemoglobin level in severe plasmodium falciparum malaria treated with artesunate in central sudan.there are few publications on anemia following artesunate treatment.201727370816
host cell remodelling in malaria parasites: a new pool of potential drug targets.when in their human hosts, malaria parasites spend most of their time housed within vacuoles inside erythrocytes and hepatocytes. the parasites extensively modify their host cells to obtain nutrients, prevent host cell breakdown and avoid the immune system. to perform these modifications, malaria parasites export hundreds of effector proteins into their host cells and this process is best understood in the most lethal species to infect humans, plasmodium falciparum. the effector proteins are syn ...201727368610
out of africa: origins and evolution of the human malaria parasites plasmodium falciparum and plasmodium vivax.plasmodium falciparum and plasmodium vivax account for more than 95% of all human malaria infections, and thus pose a serious public health challenge. to control and potentially eliminate these pathogens, it is important to understand their origins and evolutionary history. until recently, it was widely believed that p. falciparum had co-evolved with humans (and our ancestors) over millions of years, whilst p. vivax was assumed to have emerged in southeastern asia following the cross-species tra ...201727381764
development of whole sporozoite malaria vaccines.despite recent advances, malaria remains a major health threat both to populations in endemic areas as well travelers, including military personnel, to these areas. subunit vaccines have not yet achieved sufficient efficacy needed for use in any of these at risk populations. areas covered: this review discusses the current status of various whole sporozoite vaccine approaches and is mainly focused on current clinical trials. expert commentary: nearly 100% efficacy was achieved by administering m ...201727327875
assessing the reliability of microscopy and rapid diagnostic tests in malaria diagnosis in areas with varying parasite density among older children and adult patients in nigeria.current malaria control strategies are based on early diagnosis and appropriate treatment of malaria cases. the study aimed at comparing the performance of blood film microscopy and rapid diagnostic test (rdt) in plasmodium falciparum detection in patients ≥6 years of age.201727241807
antimalarial and cytotoxic quassinoids from the roots of brucea javanica.two new quassinoids, brujavanol a (1) and brujavanol b (2), along with five known quassinoids (3-7), were isolated from the roots of brucea javanica. their structures were elucidated by spectroscopic methods. the antimalarial and cytotoxic activities of the isolated compounds were also assessed. compounds 1 and 2 exhibited significant in vitro cytotoxicity against human oral cavity cancer (kb) cells with ic50 values of 1.30 and 2.36 μg/ml, respectively, whereas compound 3 showed excellent antipl ...201727380205
identification and classification of the malaria parasite blood developmental stages, using imaging flow cytometry.malaria is the most devastating parasitic disease of humans, caused by the unicellular protozoa of the plasmodium genus, such as plasmodium falciparum (pf) and is responsible for up to a million deaths each year. pf life cycle is complex, with transmission of the parasite between humans via mosquitos involving a remarkable series of morphological transformations. in the bloodstream, the parasites undergo asexual multiplications inside the red blood cell (rbc), where they mature through the ring ...201727350362
radicicol-mediated inhibition of topoisomerase vib-via activity of the human malaria parasite plasmodium falciparum.plasmodium falciparum topoisomerase vib (topovib)-topovia (topovib-via) complex can be potentially exploited as a drug target against malaria due to its absence from the human genome. previous work in our laboratory has suggested that p. falciparum topovib (pftopovib) might be a target of radicicol since treatment of parasite cultures with this antibiotic is associated with upregulation of plasmodium topovib at the transcript level as well as at the protein level. further studies demonstrated th ...201727303712
cerebral malaria treated with artemisinin in the intensive care unit: a case report.malaria is a parasitic disease that is starting to be encountered in intensive care units (icu) worldwide, owing to increasing globalisation. severe malaria caused by plasmodium falciparum, is characterised by cerebral malaria, acute renal failure, hypoglycaemia, severe anaemia, splenomegaly and alveolar oedema. we present the case of a 25-yr old male patient who presented to the emergency department of uludag university in bursa, turkey in the winter of 2014 with complaints of fever for three d ...201727095978
synergism between pfcrt and pfmdr1 genes could account for the slow recovery of chloroquine sensitive plasmodium falciparum strains in ghana after chloroquine withdrawal.unlike other countries, the chloroquine resistant marker pfcrt t76 mutant has remained fairly stable in ghana several years after official disuse of chloroquine. certain mutations in pfmdr1 may potentiate pfcrt t76, offering a possible explanation for this observation. to understand the phenomenon, the co-existence of mutations in pfmdr1 with pfcrt t76 in ghanaian plasmodium falciparum isolates was studied. the reported presence of parasites with reduced sensitivity to amodiaquine and quinine in ...201727026134
biting behaviour of anopheles funestus populations in mutare and mutasa districts, manicaland province, zimbabwe: implications for the malaria control programme.biting behaviour of anopheles funestus in mutare and mutasa districts, zimbabwe, is little understood. an investigation was conducted to primarily compare indoor and outdoor biting behaviour of the mosquito, as well as blood meal sources and sporozoite rates.201727353581
antimalarial drug resistance: an overview.malaria is a major public health burden throughout the world. resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. it is important to understand the mechanism of the antimalarial drugs, as i ...201726998432
exploring dual inhibitory role of febrifugine analogues against plasmodium utilizing structure-based virtual screening and molecular dynamic simulation.malaria is an endemic disease caused by the protozoan parasite plasomodium falciparum. febrifugine analogues are natural compound obtained from the traditional chinese herbs have shown significant antimalarial and anticancerous efficacy in experimental model. development of resistance against the existing antimalarial drug has alarmed the scientific innovators to find a potential antimalarial molecule which can be further used by endemic countries for the elimination of this disease. in this stu ...201726984239
detection of chloroquine and artemisinin resistance molecular markers in plasmodium falciparum: a hospital based study.emergence of chloroquine (cq) resistance in plasmodium falciparum has increased the morbidity and mortality of falciparum malaria worldwide. artemisinin-based combination therapies are now recommended by the world health organization as the first line treatment for falciparum malaria. numerous molecular markers have been implicated in the cq and artemisinin resistance.201726998436
monitoring the efficacy of antimalarial medicines in india via sentinel sites: outcomes and risk factors for treatment failure.to combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas.201727353588
the potential of β carbolin alkaloids to hinder growth and reverse chloroquine resistance in plasmodium falciparum.nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of plasmodium falciparum. emergence of chloroquine (cq) resistance has worsened the calamity as cq is still considered the most efficient, safe and cost effective drug among other antimalarials. this urged the scientists to search for other alternatives or sensitizers that may be able to augment cq action and reverse its resistance.201726811724
diagnosing malaria cases referred to the malaria reference laboratory in tehran university of medical science, iran.the number of malaria cases is declining worldwide; however, it remains as a serious health problem. diagnosing unusual cases is the most important issue to manage the problem. this study designed to describe the number of falciparum and vivax malaria infected patients referred to malaria reference laboratory in tehran university of medical science from 2000 to 2012.201726811720
dna sequence polymorphism of the lactate dehydrogenase genefrom iranian plasmodium vivax and plasmodium falciparum isolates.parasite lactate dehydrogenase (pldh) is extensively employed as malaria rapid diagnostic tests (rdts). moreover, it is a well-known drug target candidate. however, the genetic diversity of this gene might influence performance of rdt kits and its drug target candidacy. this study aimed to determine polymorphism of pldh gene from iranian isolates of p. vivax and p. falciparum.201726811715
hematological indices in febrile neonates with malaria parasitaemia in calabar.normal hematological indices has been determined in nigerian newborns and found to be lower compared to their caucasian counterparts. this was attributed to genetic factors. malaria is endemic in nigeria and is one of the major causes of ill health and death. anemia is an important manifestation of malaria. resistance by malaria parasites to antimalarial drug exacerbates the situation by continuous hemolysis.201726778882
dipstick urinalysis findings in children with plasmodium falciparum in the south tongu district: a case-control study.malaria ranks among the major health and developmental challenges facing some of the poorest countries in tropical and sub-tropical regions across the globe. we determined urinary abnormalities and its relationship with parasite density in children ≤12 years with plasmodium falciparum infection.201726759517
reliability of rapid diagnostic tests in diagnosing pregnancy and infant-associated malaria in nigeria.the effective management of maternal and infant malaria requires rational and prompt diagnosis. this study aims to determine the diagnostic efficiency of malaria rdt in infants and pregnant women.201726738923
in silico approach to ascertain the calcium dependent role of plasmodium falciparum sera5.the p. falciparum serine repeat antigen (pfsera5) is the most abundantly expressed protein in the parasitophorous vacuole during the asexual blood stage and serves as both drug and vaccine target. the processed central fragment (56 kda) of pfsera5 is implicated to play an important role in parasite exit (egress) during schizont rupture from erythrocytes. structural characterization of its enzymatic domain supports protease-like function for this central domain. the understanding of exact functio ...201726725489
expression of cleaved caspase-3 in renal tubular cells in plasmodium falciparum malaria patients.in plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (aki) is commonly associated with acute tubular necrosis (atn) in the kidney tissues. renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. to study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys.201726729581
prevalence of dengue viral and malaria parasitic co-infections in an epidemic district, angul of odisha, india: an eco-epidemiological and cross-sectional study for the prospective aspects of public health.the co-existence of dengue and malaria infection in an individual and the primary and secondary dengue infection during co-infection were assessed. over 1 year, 1980 blood samples were collected from suspected cases of dengue fever and analyzed by rapid diagnostic test (rdt), enzyme-linked immunosorbent assay (elisa) and polymerase chain reaction (pcr) methods to detect dengue infection. rdt and microscopic methods were used to detect malaria. of the 1980 samples, only 22 (3.0%) cases were ident ...201726653975
[evaluation of the efficacy and safety of three 2-drug combinations for the treatment of uncomplicated plasmodium falciparum malaria in senegal: artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine].since 2006, artemisinin-based combination therapies (act) have been used to treat uncomplicated plasmodium falciparum malaria in senegal, as recommended by who. recently, decreased parasite clearance with artemisinin derivatives has been reported in cambodia and thailand. the effectiveness of artemisinin derivatives in africa must be monitored. this study was conducted to evaluate the efficacy and the tolerability of three act widely used in senegal.201726644184
symmetrical peripheral gangrene: a rare complication of plasmodium falciparum malaria.malaria, the most important of the parasitic diseases of humans, is transmitted in 108 countries containing 3 billion people and causes nearly 1 million deaths each year. with the re-emergence of malaria various life-threatening complications of malaria have been observed. unarousable coma/cerebral malaria, severe normochromic, normocytic anemia, renal failure, pulmonary edema/adult respiratory distress syndrome, hypoglycemia, hypotension/shock, bleeding/disseminated intravascular coagulation (d ...201726629458
acute kidney injury in children with plasmodium falciparum malaria: determinants for mortality.♦201726429418
complicated vivax malaria, an often underestimated condition - case report.malaria is a vector-borne disease that is endemic in 91 countries. south east asia is the second most affected region in the world, with india carrying the highest burden of the disease. four species of plasmodium are known to cause malaria in humans. plasmodium vivax and plasmodium falciparum are the most common species found in india, but plasmodium malariae have also been reported. severe complications of malaria have been more commonly seen in p. falciparum infections, and those caused by p. ...201726392800
case reports on atypical presentation of plasmodium falciparum malaria in pediatric patients.variable atypical symptoms are commonly observed in malaria caused by plasmodium falciparum especially in endemic tropical nations such as india. nystagmus is observed following involvement of the cerebellum especially during the postrecovery phase. while psychotic features such as severe agitation, hallucination, paranoia may be the early symptoms of falciparum malaria among pediatric patients, urticaria with or without fever can be the initial manifestation of the disease. as the morbidity and ...201726283845
cerebral malaria complicated by blindness, deafness and extrapyramidal tract manifestation.cerebral malaria is a severe manifestation of a parasitic infection caused by plasmodium falciparum. the sequelae of this disease such as blindness, deafness, loss of motor function could be emotionally traumatic and physically disabling. we, therefore, present this case of an 8-year-old boy who presented with high-grade intermittent fever associated with multiple convulsions and prolonged coma. he regained consciousness after 12 days of treatment with intravenous quinine but was found to have b ...201726229725
plasmodium falciparum parasitaemia among booked parturients who received two doses of sulfadoxine-pyrimethamine (sp) for intermittent preventive treatment in pregnancy (iptp) in a tertiary health facility southeast nigeria.malaria is preventable but has contributed significantly to maternal morbidity and mortality in our environment. malaria parasitaemia during pregnancy is mostly asymptomatic, untreated but with complications.201726229233
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