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a malaria transmission-blocking (+)-usnic acid derivative prevents plasmodium zygote-to-ookinete maturation in the mosquito midgut.the evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. recent emergence of artemisinin resistance in southeast asia underscores the need to develop novel antimalarials and identify new targetable pathways in plasmodium parasites. transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with anti ...201627978709
targeting neutrophils to prevent malaria-associated acute lung injury/acute respiratory distress syndrome in mice.malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. when manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ali/ards). we have previously shown that a proportion of dba/2 mice infected with plasmodium berghei anka (pba) develop ali/ards and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. herein, we investig ...201627926944
in vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin.the emergence of artemisinin-resistant plasmodium falciparum strains poses a serious challenge to the control of malaria. this necessitates the development of new anti-malarial drugs. previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the p. falciparum heat-shock protein 90 (pfhsp90). the aim of this study was to test the anti-malarial activity of harmine analogues.201627903279
plasmodium falciparum and mycoplasma pneumoniae co-infection presenting with cerebral malaria manifesting orofacial dyskinesia and haemophagocytic lymphohistiocytosis.malaria is a mosquito-borne infectious disease with diverse clinical manifestations caused by a parasitic protozoan of the genus plasmodium. complex inter-relationships between mycoplasma species and plasmodium parasites have been previously noted in vitro. this is the first report of plasmodium falciparum and mycoplasma pneumoniae co-infection in a human host presenting with cerebral malaria manifesting orofacial dyskinesias and haemophagocytic lymphohistiocytosis.201627609213
phylogenetic profiles of all membrane transport proteins.in order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. proteins that are essential to survival and specific to malaria parasites are key candidates. to survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. membrane transport proteins mediate all ...201628357319
reinvestigating old pharmacophores: are 4-aminoquinolines and tetraoxanes potential two-stage antimalarials?the syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. the compounds exhibited pronounced in vitro and in vivo activity against plasmodium berghei in the thompson test. tethering a fluorine atom to the aminoquinoline c(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an ic50 = 0.31 μm and reducing the liver load in mice by up to 92% at 80 mg/kg dose. scr ...201626640981
multidrug atp-binding cassette transporters are essential for hepatic development of plasmodium sporozoites.multidrug resistance-associated proteins (mrps) belong to the c-family of atp-binding cassette (abc) transport proteins and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. rodent malaria parasites encode a single abc transporter subfamily c protein, whereas human parasites encode two: mrp1 and mrp2. although associated with drug resistance, their biological function and substrates remain unknown. to elucidate the rol ...201626332724
a novel role for von willebrand factor in the pathogenesis of experimental cerebral malaria.plasmodium falciparum malaria infection is associated with an early marked increase in plasma von willebrand factor (vwf) levels, together with a pathological accumulation of hyperreactive ultra-large vwf (ul-vwf) multimers. given the established critical role of platelets in malaria pathogenesis, these increases in plasma vwf raise the intriguing possibility that vwf may play a direct role in modulating malaria pathogenesis. to address this hypothesis, we used an established murine model of exp ...201626511133
natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes.the marine natural product (-)-8,15-diisocyano-11(20)-amphilectene (1), isolated from the caribbean sponge svenzea flava, was used as scaffold to synthetize five new products, all of which were tested against laboratory strains of plasmodium falciparum and mycobacterium tuberculosis h37rv. the scaffold contains two isocyanide units that are amenable to chemical manipulation, enabling them to be elaborated into a small library of sulfur and selenium compounds. although most of the analogs prepare ...201626748697
does calcium channel blockade have a role in prevention of expression of sepsis in renal transplant recipients?many antihypertensive agents have been demonstrated to assist in preservation of kidney function, among them those that modulate calcium channels. calcium channel blockers may also be of value in protecting hemodialysis patients from complications of sepsis. in diabetic recipients of kidney transplant allografts treated with cyclosporine, calcium channel blockade has been retrospectively linked to improved graft preservation and to fewer episodes of sepsis. this brief review outlines clinical an ...201627920569
chevalone c analogues and globoscinic acid derivatives from the fungus neosartorya spinosa kku-1nk1.four meroterpenoids, 1-hydroxychevalone c, 1-acetoxychevalone c, 1,11-dihydroxychevalone c, and 11-hydroxychevalone c and two ester epimers, 2s,4s-spinosate and 2s,4r-spinosate, together with seven known compounds, chevalones b, c, and e, tryptoquivaline, nortryptoquivaline, tryptoquivaline l, and quinadoline a were isolated from the fungus neosartorya spinosa. their structures were established based on spectroscopic data analyses. the theoretical ecd spectra of epimers, 2s,4s-spinosate and 2s,4 ...201627680770
antimicrobial molecular nanocarrier-drug conjugates.many antimicrobial drugs are poorly active against pathogenic microbes causing intracellular infections, such as mycobacterium tuberculosis or plasmodium falciparum. on the other hand, several known antimicrobial agents are not effective enough because of their limited cellular penetration. a common feature of both challenges is the inability of an active agent to cross the biological membrane(s). one of the possible approaches facing these challenges is conjugation of an active substance with a ...201627339783
total synthesis of cyclomarins a, c and d, marine cyclic peptides with interesting anti-tuberculosis and anti-malaria activities.cyclomarins are cyclic heptapeptides containing four unusual amino acids. new synthetic protocols toward their synthesis have been developed, leading to the synthesis and biological evaluation of three natural occurring cyclomarins. interestingly, cyclomarins address two completely different targets: clp c1, a subunit of the caseinolytic protease of mycobacterium tuberculosis (mtb), as well as pfap3ase of plasmodium falciparum. therefore, cyclomarins are interesting lead structures for the devel ...201627241518
evaluation of the antiplasmodial and leishmanicidal potential of myrciaria dubia (myrtaceae) extract.malaria and leishmaniasis are prevalent in tropical regions, which have environmental characteristics that are highly favorable to protozoa and vectors of these diseases; the transmission of these infections in sub-tropical regions, although recognized, represents only a small fraction of cases. plants are constantly being used in the search for and acquisition of new drugs, and many compounds derived from them have been used to combat various diseases. in this study, we evaluated the action of ...201627812653
molecular epidemiology of blood-borne human parasites in a loa loa-, mansonella perstans-, and plasmodium falciparum-endemic region of cameroon.the study of the interactions among parasites within their hosts is crucial to the understanding of epidemiology of disease and for the design of effective control strategies. we have conducted an assessment of infections with loa loa, mansonella perstans, wuchereria bancrofti, and plasmodium falciparum in eastern cameroon using a highly sensitive and specific quantitative polymerase chain reaction assay using archived dried whole blood spots. the resident population (n = 1,085) was parasitized ...201627044568
triterpenoid saponins from maesa argentea leaves.within an ongoing research program on saponins with potential antileishmanial activity, four previously undescribed saponins were isolated from maesa argentea leaves and identified by lc-ms/ms, gc-ms, and 1d and 2d nmr spectroscopy as 3β-o-{([β-d-glucopyranosyl-(1 → 2)-α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 3)]-[β-d-galactopyranosyl-(1 → 2)]-β-d-glucuronopyranosyl)}-21β-angeloyloxy-22α-butanoyloxy-13β,28-oxidoolean-16α,28α-diol (1), 3β-o-{([β-d-glucopyranosyl-(1 → 2)-α-l-rhamnopyr ...201627737476
in vitro antiprotozoal activity and cytotoxicity of extracts and isolated constituents from greenwayodendron suaveolens.the nkundo people (nkundo area of bolongo, mai-ndombe district, bandundu province, dr congo) use various plant parts of the tree greenwayodendron suaveolens (engl. & diels) verdc. (syn. polyalthia suaveolens engl. & diels) (annonaceae) against malaria, but its antiprotozoal constituents are not known.201627693770
targeting the cytochrome bc1 complex of leishmania parasites for discovery of novel drugs.endochin-like quinolones (elqs) are potent and specific inhibitors of cytochrome bc1 from plasmodium falciparum and toxoplasma gondii and show promise for novel antiparasitic drug development. to determine whether the mitochondrial electron transport chain of leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse elqs. a cohort of elqs was selectively toxic to amastigotes of leishmania mexicana and l. donovani, with 50% inh ...201627297476
in silico elucidation and inhibition studies of selected phytoligands against mitogen-activated protein kinases of protozoan parasites.parasitic mapks exhibiting significant divergence with humans and playing an imperative role in parasitic metabolic activities have been exploited from several years as important targets for development of novel therapeutics. in addition, the emergence of the drug-resistant variants of parasitic diseases in the recent years has aroused a great need for the development of potent inhibitors against them. in the present study, we selected the metabolically active mapks lmxmpk4, pfmap2 and tbmapk5 o ...201626264054
identification of "preferred" human kinase inhibitors for sleeping sickness lead discovery. are some kinases better than others for inhibitor repurposing?a kinase-targeting cell-based high-throughput screen (hts) against trypanosoma brucei was recently reported, and this screening set included the published kinase inhibitor set (pkis). from the pkis was identified 53 compounds with pec50 ≥ 6. utilizing the published data available for the pkis, a statistical analysis of these active antiparasitic compounds was performed, allowing identification of a set of human kinases having inhibitors that show a high likelihood for blocking t. brucei cellular ...201626998514
ent-pimarane and ent-kaurane diterpenes from aldama discolor (asteraceae) and their antiprotozoal activity.aldama discolor (syn.viguiera discolor) is an endemic asteraceae from the brazilian "cerrado", which has not previously been investigated for its chemical constituents and biological activity. diterpenes are common secondary metabolites found in aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. in this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2 ...201627649126
chemical and antimicrobial profiling of propolis from different regions within libya.extracts from twelve samples of propolis collected from different regions of libya were tested for their activity against trypanosoma brucei, leishmania donovani, plasmodium falciparum, crithidia fasciculata and mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. all the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of ec50 values between 1.65 and 53.6 μg/ml. the toxicity against mammalian cell ...201627195790
alkanediamide-linked bisbenzamidines are promising antiparasitic agents.a series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two trypanosoma brucei (t.b.) subspecies: t.b. brucei and t.b. rhodesiense, trypanosoma cruzi, leishmania donovani and two plasmodium falciparum subspecies: a chloroquine-sensitive strain (nf54) and a chloroquine-resistant strain (k1). the in vitro cytotoxicity was determined against rat myoblast cells (l6). seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against bot ...201627104545
highly improved antiparasitic activity after introduction of an n-benzylimidazole moiety on protein farnesyltransferase inhibitors.in our search for new protein farnesyltransferase inhibitors with improved antiparasitic activities, we modified our previously developed 3-arylthiophene series of inhibitors by replacing the thioisopropyl group by different substituted imidazolylmethanamino moieties. twenty four new derivatives were synthesized and evaluated against human and parasite farnesyltransferases, and their anti-parasitic activity was determined against plasmodium falciparum, trypanosoma brucei, trypanosoma cruzi, and ...201626774924
evaluation of in vitro antiprotozoal activity of ajuga laxmannii and its secondary metabolites.context some ajuga l. (lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. objective in the continuation of our studies on the identification of antiprotozoal secondary metabolites of turkish lamiaceae species, we have investigated the aerial parts of ajuga laxmannii. materials and methods the aerial parts of a. laxmannii were extracted with meoh. the h2o subextract was subjected to polyamide, c18-mplc an ...201626734766
recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.the 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. in this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-hda) and 2-octadecynoic acid (2-oda) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolite ...201623727443
synthesis, cytotoxic activity on leukemia cell lines and quantitative structure-activity relationships (qsar) studies of morita-baylis-hillman adducts.the morita-baylis-hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential and promising biological profiles. the morita-baylis-hillman adducts (mbha) are a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs, e.g. as anti-leishmania chagasi and leishmania amazonensis, anti- trypanosoma cruzi, anti-plasmodium falciparum and pla ...201627150963
regulatory t cells in endemic burkitt lymphoma patients are associated with poor outcomes: a prospective, longitudinal study.deficiencies in epstein-barr virus (ebv)-specific t cell immunosurveillance appear to precede the development of endemic burkitt lymphoma (ebl), a malaria-associated pediatric cancer common in sub-saharan africa. however, t cell contributions to ebl disease progression and survival have not been characterized. our objective was to investigate regulatory and inflammatory t cell responses in ebl patients associated with clinical outcomes. by multi-parameter flow cytometry, we examined peripheral b ...201628033393
antiretroviral choice for hiv impacts antimalarial exposure and treatment outcomes in ugandan children.the optimal treatment of malaria in human immunodeficiency virus (hiv)-infected children requires consideration of critical drug-drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes.201627143666
experimental systems for studying plasmodium/hiv coinfection.coinfections with human immunodeficiency virus (hiv) and plasmodium, the causative agents of aids and malaria, respectively, are frequent and their comorbidity especially in sub-saharan africa is high. while clinical studies suggest an influence of the two pathogens on the outcome of the respective infections, experimental studies on the molecular and immunological impact of coinfections are rare. this reflects the limited availability of suitable model systems that reproduce key properties of b ...201627009943
effect of hiv-1 serostatus on the prevalence of asymptomatic plasmodium falciparum parasitemia among children less than 5 years of age in benin city, nigeria.human immunodeficiency virus (hiv) infection and plasmodium falciparum malaria are 2 of the gravest health threats in sub-saharan africa. multiple repeat infections with the malaria parasite as seen in endemic areas are necessary to develop specific malaria immunity. hiv is an immunosuppressive virus and in children aged <5 years, development of malaria-specific immunity may be impaired and malaria parasite clearance in theory will be delayed; hence the predisposition to increased incidence of a ...201626908488
performance of interferon-gamma and ip-10 release assays for diagnosing latent tuberculosis infections in patients with concurrent malaria in tanzania.interferon-gamma (ifn-γ) release assays (igras) are used to detect cellular immune recognition of mycobacterium tuberculosis the chemokine ifn-γ-inducible protein 10 (ip-10) is an alternative diagnostic biomarker to ifn-γ. several conditions interfere with igra test performance. we aimed to assess the possible influence of plasmodium falciparum infection on the igra test quantiferon-tb gold® in-tube (qft) test and an in-house ip-10 release assay. in total, 241 tanzanian adults were included; 184 ...201626834199
factors influencing survival among kenyan children diagnosed with endemic burkitt lymphoma between 2003 and 2011: a historical cohort study.discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic burkitt lymphoma (ebl) in resource-constrained settings has recaptured international attention. using multivariate analyses, we evaluated 428 children with ebl in kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (ldh), epstein-barr virus (ebv) and plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotr ...201627136063
impact of plasmodium falciparum coinfection on longitudinal epstein-barr virus kinetics in kenyan children.endemic burkitt lymphoma is associated with epstein-barr virus (ebv) and plasmodium falciparum coinfection, although how p. falciparum exposure affects the dynamics of ebv infection is unclear. we have used a modeling approach to study ebv infection kinetics in a longitudinal cohort of children living in regions of high and low malaria transmission in kenya. residence in an area of high malaria transmission was associated with a higher rate of ebv expansion during primary ebv infection in infant ...201626531246
antibody-guided vaccine design: identification of protective epitopes.in the last decade, progress in the analysis of the human immune response and in the isolation of human monoclonal antibodies have provided an innovative approach to the identification of protective antigens which are the basis for the design of vaccines capable of eliciting effective b-cell immunity. in this review we illustrate, with relevant examples, the power of this approach that can rapidly lead to the identification of protective antigens in complex pathogens, such as human cytomegalovir ...201627343848
the genome of haemoproteus tartakovskyi and its relationship to human malaria parasites.the phylogenetic relationships among hemosporidian parasites, including the origin of plasmodium falciparum, the most virulent malaria parasite of humans, have been heavily debated for decades. studies based on multiple-gene sequences have helped settle many of these controversial phylogenetic issues. however, denser taxon sampling and genome-wide analyses are needed to confidently resolve the evolutionay relationships among hemosporidian parasites. genome sequences of several plasmodium parasit ...201627190205
cloning, expression, purification and characterization of plasmodium spp. glyceraldehyde-3-phosphate dehydrogenase.plasmodium spp. solely rely on glycolysis for their energy needs during asexual multiplication in human rbcs, making the enzymes of this pathway potential drug targets. we have cloned, over-expressed and purified plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase (pfgapdh) for its kinetic and structural characterization. ∼ 30-40 mg pure recombinant enzyme with a specific activity of 12.6 units/mg could be obtained from a liter of escherichia coli culture. this enzyme is a homotetrame ...201626341815
can mutations in the gene encoding transcription factor eklf (erythroid krüppel-like factor) protect us against infectious and parasitic diseases?transcription factor eklf (erythroid krüppel-like factor) belongs to the group of krüppellike factors, which regulate proliferation, differentiation, development and apoptosis of mammalian cells. eklf factor is present in erythroid cells, where it participates in regulation of hematopoiesis, expression of genes encoding transmembrane proteins (including blood group antigens), and heme biosynthesis enzymes. it is also a key factor in downregulation of γ-globins and activation of β-globin gene exp ...201627708211
production of recombinant proteins from plasmodium falciparum in escherichia coli.the production of recombinant proteins is essential for the characterization and functional study of proteins from plasmodium falciparum. however, the proteins of p. falciparum are among the most challenging to express, and when expression is achieved, the recombinant proteins usually fold incorrectly and lead to the formation of inclusion bodies.201627622630
phagocytosis-inducing antibodies to plasmodium falciparum upon immunization with a recombinant pfemp1 nts-dbl1α domain.individuals living in endemic areas gradually acquire natural immunity to clinical malaria, largely dependent on antibodies against parasite antigens. there are many studies indicating that the variant antigen pfemp1 at the surface of the parasitized red blood cell (prbc) is one of the major targets of the immune response. it is believed that antibodies against pfemp1 confer protection by blocking sequestration (rosetting and cytoadherence), inducing antibody-dependent cellular-inhibitory effect ...201627531359
crystal structure of truncated aspartate transcarbamoylase from plasmodium falciparum.the de novo pyrimidine-biosynthesis pathway of plasmodium falciparum is a promising target for antimalarial drug discovery. the parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. direct (or indirect) inhibition of de novo pyrimidine biosynthesis via dihydroorotate dehydrogenase (pfdhodh), the fourth enzyme of the pathway, has already been shown to be lethal to the parasite. in the second step of the plasmodial py ...201627380369
[cloning, expression and identification of gametocyte specific protein pfgdv1 of plasmodium falciparum].to clone a gametocyte specific protein pfgdv1 of plasmodium falciparum, express and identify recombinant pfgdvl protein in vitro.201627356402
intranasal immunization with a peptide conjugated to salmonella flagellin induces both systemic and mucosal peptide-specific antibody responses in mice.in this study, the mucosal adjuvant activity of salmonella flagellin as a carrier in a conjugate of exp153-rflic was investigated. exp153-rflic was made by conjugation of a synthetic b-cell epitope peptide derived from plasmodium falciparum exported protein-1(exp153) to recombinant phase 1 flagellin of salmonella enterica serovar typhimurium expressed in escherichia coli (rflic), and used to immunize balb/c mice via intranasal instillation. it was found that robust exp153-specific serum igg anti ...201627301339
an epidemiologically successful escherichia coli sequence type modulates plasmodium falciparum infection in the mosquito midgut.malaria transmission relies on the successful development of plasmodium parasites in the anopheles mosquito vector. within the mosquito midgut, malaria parasites encounter a resident bacterial flora and parasite-bacteria interactions modulate plasmodium development. the mechanisms by which the bacteria interact with malaria parasites are still unknown. the intestinal microbiota could regulate immune signaling pathways or produce bacterial compounds that block plasmodium development. in this stud ...201627154329
cloning, overexpression, purification and immunolocal-ization of pfd0975w from the malaria parasite plasmodium falciparum.malaria is a parasitic disease, widespread along the tropical regions of the world. the disease has killed 4, 38,000 individuals in the year 2015 (who). the malaria parasite, plasmodium falciparum, has evolved resistance to front-line antimalarials over the decade, necessitating the identification of new drug targets. protein kinases are excellent drug targets since they participate in critical cell-signaling cascades. we have identified a putative rio-like protein kinase, pfd0975w, from the pla ...201627150807
salmonella flagellin acted as an effective fusion partner for expression of plasmodium falciparum surface protein 25 in escherichia coli.plasmodium falciparum surface protein 25 (pfs25) is a hard-to-express and hard-to-solubilize protein in escherichia coli. to overcome this problem, the phase 1 flagellin of salmonella enterica serovar typhimurium (flic) was used as a fusion partner for pfs25. the fusion expression of pfs25 with flic greatly enhanced the expression level and solubility of pfs25 in e. coli bl21(de3). the ni-purified fusion protein of flic-pfs25 was recognized by two anti-pfs25 monoclonal antibodies. by comparison, ...201627058511
use of a chimeric hsp70 to enhance the quality of recombinant plasmodium falciparum s-adenosylmethionine decarboxylase protein produced in escherichia coli.s-adenosylmethionine decarboxylase (pfadometdc) from plasmodium falciparum is a prospective antimalarial drug target. the production of recombinant pfadometdc for biochemical validation as a drug target is important. the production of pfadometdc in escherichia coli has been reported to result in unsatisfactory yields and poor quality product. the co-expression of recombinant proteins with molecular chaperones has been proposed as one way to improve the production of the former in e. coli. e. col ...201627031344
n-terminal methionine processing by the zinc-activated plasmodium falciparum methionine aminopeptidase 1b.the methionine aminopeptidase 1b from plasmodium falciparum (pfmetap 1b) was cloned, expressed in escherichia coli and characterized. surprisingly, and in contrast to other methionine aminopeptidases (metaps) that require heavy-metal cofactors such as cobalt, the enzyme is reliably activated by zinc ions. immobilization of the enzyme is possible by his-tag metal chelation to iminodiacetic acid-agarose and by covalent binding to chloroacetamido-hexyl-agarose. the covalently immobilized enzyme sho ...201627023914
differential t-cell responses to a chimeric plasmodium falciparum antigen; ub05-09, correlates with acquired immunity to malaria.the development of a sterilizing and cost-effective vaccine against malaria remains a major problem despite recent advances. in this study, it is demonstrated that two antigens of p. falciparum ub05, ub09 and their chimera ub05-09 can serve as protective immunity markers by eliciting higher t-cell responses in malaria semi-immune subjects (sis) than in frequently sick subjects (fss) and could be used to distinguish these two groups. ub05, ub09 and ub05-09 were cloned, expressed in e. coli, purif ...201627012849
contraceptive efficacy of recombinant fusion protein comprising zona pellucida glycoprotein-3 fragment and gonadotropin releasing hormone.contraceptive vaccines have been used for the management of wildlife population. in the present study, we have examined the contraceptive potential of escherichia coli-expressed recombinant fusion protein comprising of 'promiscuous' t cell epitope of tetanus toxoid [tt; amino acid (aa) residues 830-844] followed by dilysine linker (kk), dog zp3 fragment (aa residues 307-346), triglycine spacer (ggg), t cell epitope of bovine rnase (brnase; aa residues 94-104), gnrh, t cell epitope of circumsporo ...201626859695
soluble recombinant merozoite surface antigen-142kda of plasmodium vivax: an improved diagnostic antigen for vivax malaria.enzyme linked immunosorbent assay (elisa), as a serological test, can be a beneficial tool for epidemiological studies by screening blood donors and diagnosis of specific antibodies from plasmodium vivax (p. vivax) infected cases. since p. vivax cannot easily be acquired in vitro, elisa assays using total or semi-purified antigens are seldom used. on the basis of this restriction, we examined whether recombinant protein 42 kda related to c-terminal region of the merozoite surface antigen-1 of p. ...201626851675
genetic diversity and natural selection in the rhoptry-associated protein 1 (rap-1) of recent plasmodium knowlesi clinical isolates from malaysia.the plasmodium rhoptry-associated protein 1 (rap-1) plays a role in the formation of the parasitophorous vacuole following the parasite's invasion of red blood cells. although there is some evidence that the protein is recognized by the host's immune system, study of plasmodium falciparum rap-1 (pfrap-1) suggests that it is not under immune pressure. a previous study on five old (1953-1962) p. knowlesi strains suggested that rap-1 has limited genetic polymorphism and might be under negative sele ...201626847346
a multilayer network approach for guiding drug repositioning in neglected diseases.drug development for neglected diseases has been historically hampered due to lack of market incentives. the advent of public domain resources containing chemical information from high throughput screenings is changing the landscape of drug discovery for these diseases. in this work we took advantage of data from extensively studied organisms like human, mouse, e. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate drug targets in negle ...201626735851
expression, purification and characterization of plasmodium falciparum vacuolar protein sorting 29.translocation of various proteins to the subcellular organelles is an essential mechanism to regulate the metabolic pathways and often vacuolar protein sorting (vps) proteins are involved in this transportation. plasmodium falciparum vps29 (pfvps29) is predicted to be a functional component in the assembly of the retromer complex; however, so far detailed characterization of pfvps29 in its native form is not yet done. we report the successful expression and purification of tag-free recombinant p ...201626690372
biologically active acetylenic amino alcohol and n-hydroxylated 1,2,3,4-tetrahydro-β-carboline constituents of the new zealand ascidian pseudodistoma opacum.the first occurrence of an acetylenic 1-amino-2-alcohol, distaminolyne a (1), isolated from the new zealand ascidian pseudodistoma opacum, is reported. the isolation and structure elucidation of 1 and assignment of absolute configuration using the exciton coupled circular dichroism technique are described. in addition, a new n-9 hydroxy analogue (2) of the known p. opacum metabolite 7-bromohomotrypargine is also reported. antimicrobial screening identified modest activity of 1 toward escherichia ...201626670413
structural and functional characterization of plasmodium falciparum nicotinic acid mononucleotide adenylyltransferase.nicotinic acid mononucleotide adenylyltransferase (namnat) is an indispensable enzyme for the synthesis of nad and nad phosphate. it catalyzes the adenylylation of nicotinic acid mononucleotide (namn) to yield nicotinic acid adenine dinucleotide (naad). since nad(h) and nad phosphate(h) are essentially involved in metabolic and redox regulatory reactions, namnat is an attractive drug target in the fight against bacterial and parasitic infections. notably, namnat of the malaria parasite plasmodiu ...201627984041
new triterpenoidal saponins from koelreuteria paniculata.bioassay guided fractionation and chemical investigation of the ethanolic extract of the aerial parts of koelreuteria paniculata laxm. (sapindaceae), resulted in the isolation and identification of three new triterpenoid saponins 1-3 named paniculatosoid a-c, along with eleven known compounds. the structures of the isolated compounds were elucidated using 1d and 2d nmr experiments, hresims, and comparison with literature data. the occurrence of tridesmosidic saponin is reported for the first tim ...201628250867
entamoeba histolytica induces human neutrophils to form nets.entamoeba histolytica invades the intestine and other organs during the pathogenesis of amoebiasis. in the early stages, the host organism responds with an inflammatory infiltrate composed mostly of neutrophils. it has been reported that these immune cells, activated by e. histolytica, exert a protective role by releasing proteolytic enzymes and generating reactive oxygen/nitrogen species (ros/rns) and antimicrobial peptides. it is now known that neutrophils also produce neutrophil extracellular ...201627138813
protozoan parasites.• stool antigen detection for cryptosporidium sp, giardia lamblia and entamoeba histolytica are now commercially available, have better sensitivity and specificity than the traditional stool microscopy, and are less dependent on personnel skill. tests employing newer techniques with faster turnaround time are also available for diagnosing trichomoniasis.• nitazoxanide, the only u.s. food and drug administration-approved medication for therapy of cryptosporidiosis, is effective among immunocompet ...201626834225
automated device for asynchronous extraction of rna, dna, or protein biomarkers from surrogate patient samples.many biomarker-based diagnostic methods are inhibited by nontarget molecules in patient samples, necessitating biomarker extraction before detection. we have developed a simple device that purifies rna, dna, or protein biomarkers from complex biological samples without robotics or fluid pumping. the device design is based on functionalized magnetic beads, which capture biomarkers and remove background biomolecules by magnetically transferring the beads through processing solutions arrayed within ...201626194105
a case of an avoidable admission to an ebola treatment unit with malaria and an associated heat illness.we present a 27-year old british nurse admitted to the kerry town ebola treatment unit, sierra leone, with symptoms fitting suspect-ebola virus disease (evd) case criteria. a diagnosis of plasmodium falciparum malaria and heat illness was ultimately made, both of which could have been prevented through employing simple measures not utilised in this case. the dual pathology of her presentation was atypical for either disease meaning evd could not be immediately excluded. she remained isolated in ...201626141211
regulation of dna replication proteins in parasitic protozoans: possible role of cdk-like kinases.regulatory roles of cdks in fundamental processes including cell cycle progression and transcription are well conserved in metazoans. this family of proteins has undergone significant evolutionary divergence and specialization. several cdk-like kinases have been identified and characterized in parasitic protozoans. however, clear functional role and physiological relevance of these proteins in protozoans still remain elusive. in continuation with the recent finding that cdk-like protein pfpk5 re ...201626780367
screening of the open source malaria box reveals an early lead compound for the treatment of alveolar echinococcosis.the metacestode (larval) stage of the tapeworm echinococcus multilocularis causes alveolar echinococcosis (ae), a very severe and in many cases incurable disease. to date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some pati ...201626967740
prevalence of zoonotic and vector-borne infections among afghan national army recruits in afghanistan.to measure prevalence of prior/current plasmodium vivax and plasmodium falciparum (pv and pf), brucella spp. (br), dengue virus (denv), leishmania donovani (visceral leishmaniasis; vl), and crimean-congo hemorrhagic fever (cchf) virus exposure among afghan national army (ana) recruits.201627304051
[detection of echinococcus granulosus and echinococcus multilocularis in cyst samples using a novel single tube multiplex real-time polymerase chain reaction].cystic echinococcosis (ce) and alveolar echinococcosis (ae) caused by echinococcus granulosus and echinococcus multilocularis, respectively, are important helminthic diseases worldwide as well as in our country. epidemiological studies conducted in turkey showed that the prevalence of ce is 291-585/100.000. it has also been showed that the seroprevalence of ae is 3.5%. for the diagnosis of ce and ae, radiological (ultrasonography, computed tomography, magnetic resonance) and serological methods, ...201627175499
novel bumped kinase inhibitors are safe and effective therapeutics in the calf clinical model for cryptosporidiosis.cryptosporidiosis, caused by the apicomplexan parasite cryptosporidium parvum, is a diarrheal disease that has produced a large global burden in mortality and morbidity in humans and livestock. there are currently no consistently effective parasite-specific pharmaceuticals available for this disease. bumped kinase inhibitors (bkis) specific for parasite calcium-dependent protein kinases (cdpks) have been shown to reduce infection in several parasites having medical and veterinary importance, inc ...201627923949
drug repurposing: mining protozoan proteomes for targets of known bioactive compounds.to identify potential opportunities for drug repurposing by developing an automated approach to pre-screen the predicted proteomes of any organism against databases of known drug targets using only freely available resources.201623757409
production of new cladosporin analogues by reconstitution of the polyketide synthases responsible for the biosynthesis of this antimalarial agent.the antimalarial agent cladosporin is a nanomolar inhibitor of the plasmodium falciparum lysyl-trna synthetase, and exhibits activity against both blood- and liver-stage infection. cladosporin can be isolated from the fungus cladosporium cladosporioides, where it is biosynthesized by a highly reducing (hr) and a non-reducing (nr) iterative type i polyketide synthase (pks) pair. genome sequencing of the host organism and subsequent heterologous expression of these enzymes in saccharomyces cerevis ...201626783060
the synthesis and biological evaluation of alkyl and benzyl naphthyridinium analogs of eupolauridine as potential antimicrobial and cytotoxic agents.eupolauridine, an indenonaphthyridine alkaloid, has been previously reported by us to exhibit antifungal activity. this study describes the synthesis of new alkyl and benzyl naphthyridinium/pyridinium analogs of eupolauridine as potential antifungal agents. a majority of the analogs exhibited antifungal activity against opportunistic pathogens such as candida albicans and cryptococcus neoformans. several of them were also effective against bacteria (staphylococcus aureus, mrs, pseudomonas and my ...201627769668
chemodiversity associated with cytotoxicity and antimicrobial activity of piper aduncum var. ossanum.chemical analysis, antimicrobial activity and cytotoxic effects of essential oils (eos) from leaves of piper aduncum var. ossanum from two localities bauta (eo-b) and ceiba (eo-c), artemisa province, cuba, were determined. eos were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. eo-b demonstrated higher activity against s. aureus and l. amazonensis; while a lower cytotoxicity on mammalian cells was observed. both eos displayed the same activity against plasmod ...201627603914
biological activities of croton palanostigma klotzsch.different species of croton are used in traditional amazonian medicine. among the popular uses are treatment of bacterial diseases, poorly healing wounds and fevers.201627041867
novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: synthesis, antibacterial, antitubercular and antimalarial activities.a series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. the newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against mycobacterium tuberculosis h37rv and antimalarial activity against plasmodium falciparum. most of them exhibited significant antibacterial activity as compared to the first line dru ...201626900659
tetrandrine--a molecule of wide bioactivity.stephania tetrandra and other related species of menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. the plant is extensively referenced in the chinese pharmacopoeia for its use in the chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. tetrandrine, well-known to act as a calcium channel blocker, h ...201626899361
evaluation of quantum dot immunofluorescence and a digital cmos imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays.organic fluorescent dyes are widely used for the visualization of bound antibody in a variety of immunofluorescence assays. however, the detection equipment is often expensive, fragile, and hard to deploy widely. quantum dots (qdot) are nanocrystals made of semiconductor materials that emit light at different wavelengths according to the size of the crystal, with increased brightness and stability. here, we have evaluated a small benchtop "personal" optical imager (arraycam) developed for quanti ...201626842269
eco-friendly drugs from the marine environment: spongeweed-synthesized silver nanoparticles are highly effective on plasmodium falciparum and its vector anopheles stephensi, with little non-target effects on predatory copepods.mosquitoes act as vectors of devastating pathogens and parasites, representing a key threat for millions of humans and animals worldwide. the control of mosquito-borne diseases is facing a number of crucial challenges, including the emergence of artemisinin and chloroquine resistance in plasmodium parasites, as well as the presence of mosquito vectors resistant to synthetic and microbial pesticides. therefore, eco-friendly tools are urgently required. here, a synergic approach relying to nanotec ...201627180838
characterization of a papain-like cysteine protease essential for the survival of babesia ovis merozoites.babesia ovis, a tick-transmitted intraerythrocytic protozoan parasite, causes severe infections in small ruminants from southern europe, middle east, and northern africa. with the aim of finding potential targets for the development of control methods against this parasite, sequence analysis of its genome led to the identification of four putative cysteine proteases of the c1a family. orthology between b. ovis, b. bovis, t. annulata, and t. parva sequences showed that each b. ovis c1a peptidase ...201626456355
detection and management of the first human anthrax outbreak in togo.the aim of this study was to describe and define an outbreak of human anthrax in two villages in the northern savannah region of togo.201626672006
antimicrobial compounds from endophytic streptomyces sp. bcc72023 isolated from rice (oryza sativa l.).an endophytic actinomycete strain bcc72023 was isolated from rice (oryza sativa l.) and identified as the genus streptomyces, based on phenotypic, chemotaxonomic and 16s rrna gene sequence analyses. the strain showed 99.80% similarity compared with streptomyces samsunensis m1463(t). chemical investigation led to the isolation of three macrolides, efomycins m (1), g (2) and oxohygrolidin (3), along with two polyethers, abierixin (4) and 29-o-methylabierixin (5). to our knowledge, this is the firs ...201626809052
monoclonal antibodies that recognize the alkylation signature of antimalarial ozonides oz277 (arterolane) and oz439 (artefenomel).the singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides oz277 (arterolane) and oz439 (artefenomel). despite the critical importance of artemisinin combination therapies (acts), the precise mode of action of peroxidic antimalarials is not fully understood. however, it has long been proposed that the peroxide bond in artemisinin ...201626819968
malaria in children of tshimbulu (western kasai, democratic republic of the congo): epidemiological data and accuracy of diagnostic assays applied in a limited resource setting.the literature data on malaria in western kasai, drc, are limited and inadequate. a recent molecular survey there has detected plasmodium ovale and plasmodium malariae as mixed infections with plasmodium falciparum. in tshimbulu, western kasai, during a humanitarian initiative designed to provide children with free preventive screening and to reduce the local high malaria death rate, accurate species identification was performed, in order to collect unambiguous epidemiological data and to evalua ...201626864461
a new lumazine peptide penilumamide e from the fungus aspergillus terreus.a new rare lumazine peptide, penilumamide e (1), together with 13 known compounds (2-14) were isolated from the fungus aspergillus terreus. their structures were identified by spectroscopic techniques. the relative configuration of 1 was confirmed by single-crystal x-ray diffraction analysis. compound 10 exhibited antimalarial activity against plasmodium falciparum with ic50 values of 2.83 μg/ml. compounds 4 and 6 showed weak cytotoxicity against cholangiocarcinoma (cca) cell lines. in addition, ...201626518160
identification of interchangeable cross-species function of elongation factor-1 alpha promoters in babesia bigemina and babesia bovis.tick-borne babesia bigemina is responsible for acute and potentially lethal hemolytic disease in cattle. the development of genetic manipulation tools necessary to the better understanding of parasite biology is currently limited by the lack of a complete parasite genome and experimental tools such as transfection. effective promoters, required to regulate expression of transgenes, such as the elongation factor-1 alpha (ef-1α), have been identified in other apicomplexans such as babesia bovis an ...201627835993
replication and maintenance of the plasmodium falciparum apicoplast genome.members of the phylum apicomplexa are responsible for many devastating diseases including malaria (plasmodium spp.), toxoplasmosis (toxoplasma gondii), babesiosis (babesia bovis), and cyclosporiasis (cyclospora cayetanensis). most apicomplexans contain a unique and essential organelle called the apicoplast. derived from an ancient chloroplast, the apicoplast replicates and maintains a 35 kilobase (kb) circular genome. due to its essential nature within the parasite, drugs targeted to proteins in ...201627338018
interactions between gastrointestinal nematodes and malaria in a cohort of children in an amazonian village.most studies on nematode-malaria interactions were conducted outside of the americas. the objective of the present study was thus to study the relation between malaria and nematodes in a cohort of children in an amazonian village.201627694323
plasmodium falciparum and soil-transmitted helminth co-infections among children in sub-saharan africa: a systematic review and meta-analysis.the epidemiology of soil-transmitted helminth (sth) and plasmodium co-infections need better understanding. the findings of the individual studies are inconclusive. a systematic review was conducted to synthesize evidence on the association of sth infection with the prevalence and density of plasmodium falciparum infection, and its effect on anaemia among children in sub-saharan africa (ssa).201627306987
evolutionary immune response to conserved domains in parasites and aeroallergens.the immune response based on immunoglobulin e (ige) evolved as a defense against specific parasitic infections. in the absence of active helminthic infections, the immune system has redirected its ige epitopes toward innocuous environmental antigens. helminths and aeroallergens have a similar stereotypical ige response to unique antigens that can not be explained by chance alone. this study was designed to evaluate potential homology between conserved protein domains embedded in parasitic organi ...201623406942
a plant-based transient expression system for the rapid production of malaria vaccine candidates.there are currently no vaccines that provide sterile immunity against malaria. various proteins from different stages of the plasmodium falciparum life cycle have been evaluated as vaccine candidates, but none of them have fulfilled expectations. therefore, combinations of key antigens from different stages of the parasites life cycle may be essential for the development of efficacious malaria vaccines. following the identification of promising antigens using bioinformatics, proteomics, and/or i ...201627076325
synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities.the present study was carried out in an attempt to synthesize a new class of antimicrobial and antiplasmodial agents by copper catalyzed click chemistry to afford 25 compounds 10-14(a-e) of 1,4-disubstituted-1,2,3-triazole derivatives of chalcones and flavones. the structures of the newly synthesized compounds were established by elemental analysis, ir, (1)h nmr, (13)c nmr and mass spectral data. the newly synthesized compounds were evaluated for their antibacterial activity against gram positiv ...201626922227
antimicrobial compounds from root, stem bark and seeds of melia volkensii.three compounds, toosendanin (1), kulactone (2) and scopoletin (3), were isolated from either the root bark and/or the stem bark of melia volkensii. their structures were determined on the basis of spectroscopic data generated and by comparison with data from the literature. 1 and 2, isolated for the first time from m. volkensii, exhibited significant (p < 0.05) activity against escherichia coli with minimum inhibitory concentration of 12.5 μg/ml, close to that of neomycin (6.25 μg/ml). the comp ...201626517430
infectious cause of death determination using minimally invasive autopsies in developing countries.in developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and treatment guidelines. we aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (mia) procedures and to assess their performance. thirty mias performed in adults at maputo central hospital in southern mozambique were included in the ana ...201626508103
mechanism of artemisinin resistance for malaria pfatp6 l263 mutations and discovering potential antimalarials: an integrated computational approach.artemisinin resistance in plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. several studies have associated mutations in the pfatp6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. associated mutations act as a biomarker to measure the artemisinin efficacy. in the proposed work, we have analyzed the binding affinity and efficacy between pfatp6 and artemisinin in the presence of ...201627471101
identification of plasmodium falciparum translation initiation eif2β subunit: direct interaction with protein phosphatase type 1.protein phosphatase 1 (pp1c) is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. here, we report that eukaryotic initiation factor 2β of plasmodium falciparum (pfeif2β) is an interactor of pfpp1c. sequence analysis of pfeif2β revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to pfpp1 ((29)fgekkk(34), (103)kvaw(106)). as expec ...201627303372
characteristics of imported malaria and species of plasmodium involved in shandong province, china (2012-2014).malaria remains a serious public health problem in shandong province, china; therefore, it is important to explore the characteristics of the current malaria prevalence situation in the province. in this study, data of malaria cases reported in shandong during 2012-2014 were analyzed, and plasmodium species were confirmed by smear microscopy and nested-pcr. a total of 374 malaria cases were reported, 80.8% of which were reported from 6 prefectures. of all cases, p. falciparum was dominant (81.3% ...201627658591
the increasing importance of plasmodium ovale and plasmodium malariae in a malaria elimination setting: an observational study of imported cases in jiangsu province, china, 2011-2014.following initiation of china's national malaria elimination action plan in 2010, indigenous malaria infections in jiangsu province decreased significantly. meanwhile imported plasmodium infections have increased substantially, particularly plasmodium ovale and plasmodium malariae. given the risk for malaria resurgence, there is an urgent need to understand the increase in imported p. ovale and p. malariae infections as china works to achieve national malaria elimination.201627604629
localization and interactions of plasmodium falciparum swib/mdm2 homologues.malaria remains a global health problem and the majority of deaths are caused by plasmodium falciparum parasites. due to the rapid emergence of drug-resistant strains, novel avenues of research on the biology of the parasite are needed. the massive proliferation of asexual, intra-erythrocytic parasites every 48 h could kill the human host prior to transmission of slow-developing gametocytes to the mosquito vector. a self-induced p. falciparum programmed cell death mechanism has been hypothesized ...201626791088
household clustering of asymptomatic malaria infections in xepon district, savannakhet province, lao pdr.in the lao pdr, malaria morbidity and mortality have remarkably decreased over the past decade. however, asymptomatic infections in rural villages contribute to the on-going local transmission. the primary objective of this study was to explore the characteristics of infections in a malaria-endemic district of the lao pdr. the specific objectives were to investigate the prevalence and species of malaria parasites using molecular methods and to assess individual and household parasite levels and ...201627756391
biochemical and functional characterization of plasmodium falciparum dna polymerase δ.emergence of drug-resistant plasmodium falciparum has created an urgent need for new drug targets. dna polymerase δ is an essential enzyme required for chromosomal dna replication and repair, and therefore may be a potential target for anti-malarial drug development. however, little is known of the characteristics and function of this p. falciparum enzyme.201626911594
protective efficacy of plasmodium vivax radiation-attenuated sporozoites in colombian volunteers: a randomized controlled trial.immunizing human volunteers by mosquito bite with radiation-attenuated plasmodium falciparum sporozoites (ras) results in high-level protection against infection. only two volunteers have been similarly immunized with p. vivax (pv) ras, and both were protected. a phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of pvras immunization.201627760143
associations between season and gametocyte dynamics in chronic plasmodium falciparum infections.in a markedly seasonal malaria setting, the transition from the transmission-free dry season to the transmission season depends on the resurgence of the mosquito population following the start of annual rains. the sudden onset of malaria outbreaks at the start of the transmission season suggests that parasites persist during the dry season and respond to either the reappearance of vectors, or correlated events, by increasing the production of transmission stages. here, we investigate whether pla ...201627870874
evaluation of the operational challenges in implementing reactive screen-and-treat and implications of reactive case detection strategies for malaria elimination in a region of low transmission in southern zambia.as malaria transmission declines in many regions of sub-saharan africa, interventions to identify the asymptomatic reservoir are being deployed with the goals of improving surveillance and interrupting transmission. reactive case detection strategies, in which individuals with clinical malaria are followed up at their home and household residents and neighbours are screened and treated for malaria, are increasingly used as part of malaria elimination programmes.201627527347
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