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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
post-plasmodium vivax malaria cerebellar ataxia and optic neuritis: a new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?acute disseminated encephalomyelitis (adem) is commonly seen after viral and bacterial infections, immunization, and plasmodium falciparum (pf) malaria. plasmodium vivax (pv) rarely causes adem. we report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from pv. magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of adem. no specific viral etiology was found on cerebrospinal fluid exa ...201725878748
severe malaria complicated by g6pd deficiency in a pediatric tanzanian immigrant.approximately 1,500 cases of malaria are diagnosed in the united states each year. most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers returning from the developing world, so vigilance by providers is needed when evaluating patients returning from areas in which malaria is endemic. despite the availability of effective treatment, malaria ...201725762879
autopsy study of febrile deaths during monsoon at a tertiary care institute in india: is malaria still a challenge?to utilise an autopsy-based approach to study the febrile deaths and deaths due to malaria during monsoon period of three years at a tertiary care teaching hospital in mumbai, india.201725657486
uncommon neurological manifestations of a common tropical vector borne disease.malaria poses a major public health problem in india, where it is endemic, especially severe malaria caused by plasmodium falciparum infestation. there have been great changes in the clinical manifestation of severe falciparum malaria over the past couple of decades, with a shift from cerebral malaria to fever with jaundice, renal failure, bleeding diathesis, and multi-organ dysfunction syndrome. here, we discuss two cases of severe falciparum malaria which presented with extremely uncommon neur ...201725709956
genome-wide significant linkage to igg subclass responses against plasmodium falciparum antigens on chromosomes 8p22-p21, 9q34 and 20q13.a genome-wide scan was conducted for the levels of total immunoglobulin g (igg) and igg subclasses directed against plasmodium falciparum antigens in an urban population living in burkina faso. non-parametric multipoint linkage analysis provided three chromosomal regions with genome-wide significant evidence (logarithm of the odds (lod) score >3.6), and five chromosomal regions with genome-wide suggestive evidence (lod score >2.2). igg3 levels were significantly linked to chromosomes 8p22-p21 an ...201725521226
genetic polymorphisms associated with sulphadoxine-pyrimethamine drug resistance among plasmodium falciparum field isolates in malaria endemic areas of assam.the emergence of antimalarial drug resistance malaria parasite is widespread in north eastern region of india. during january 2012-december 2013, we conducted active surveillance for detection of antifolate resistance-associated genetic polymorphisms in plasmodium falciparum malaria parasite from different malaria endemic areas of assam.201725511211
the origin of behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection.it is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. behçet's disease (bd) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. we carried out a review of published data to draw up an evolutionary adaptation model, as author's pe ...201724447390
genetic diversity of plasmodium vivax and plasmodium falciparum in kohat district, pakistan.malaria is one of the serious diseases threatening human health in pakistan and contributes to a large proportion of the total malaria deaths in south asia. however, little is known about the nature and extent of genetic diversity of the malarial parasites circulating in pakistan. this study was designed to assess the infection status of plasmodium and the genetic diversity of plasmodium vivax and plasmodium falciparum by analyzing msp-3α, msp-3β and msp-1, msp-2 genes respectively using allele ...201722552463
cerebral malaria: mysteries at the blood-brain barrier.cerebral malaria is the most severe pathology caused by the malaria parasite, plasmodium falciparum. the pathogenic mechanisms leading to cerebral malaria are still poorly defined as studies have been hampered by limited accessibility to human tissues. nevertheless, histopathology of post-mortem human tissues and mouse models of cerebral malaria have indicated involvement of the blood-brain barrier in cerebral malaria. in contrast to viruses and bacteria, malaria parasites do not infiltrate and ...201722460644
contribution of plasmodium knowlesi to multi-species human malaria infections in north sumatera, indonesia. 201728201638
adaptive immunity is essential in preventing recrudescence of plasmodium yoelii malaria parasites after artesunate treatment.artemisinin-based antimalarials, such as artesunate (art), alone or in combination, are the mainstay of the therapy against malaria caused by plasmodium falciparum. however, the emergence and spread of artemisinin resistance threatens the future success of its global malaria eradication. although much of the reported artemisinin resistance can be attributed to mutations intrinsic to the parasite, a significant proportion of treatment failures are thought to be due to other factors such as the ho ...201728664674
malaria and severe anemia over eight years at gambo rural hospital, southern ethiopia.evolution of incident malaria and frequency of anemia were analyzed over eight years in a rural hospital in southern ethiopia. capillary blood samples were tested for hemoglobin concentration, and in some instances for malaria parasites, at gambo rural general hospital between january 2007 and september 2014, and the results recorded. main demographic data were also recorded in subjects with plasmodium sp. infections. of a total of 54,493 blood samples taken from 45,096 different patients, 21,72 ...201728502227
plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.antigenic variation in malaria was discovered in plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (m. mulatta). the variant proteins, known as the p. knowlesi schizont infected cell agglutination (sica) antigens and the p. falciparum erythrocyte membrane protein 1 (pfemp1) antigens, expressed by the sicavar and var multigene families, respectively, have been studied for over 30 years. expression of the sica antigens in p. knowlesi requires a splenic component, and ...201728712361
safety, immunogenicity, and cross-species protection of a plasmid dna encoding plasmodium falciparum sera5 polypeptide, microbial epitopes and chemokine genes in mice and olive baboons.incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. the present study sought to determine safety, immunogenicity and cross-species efficacy ofplasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of bacille-calmette guerin (bcg), tetanus toxoid (tt) and a chemokine gene. olive baboons and balb/c mice were randomly assigned into vaccine and control groups. the vaccine group anima ...201728808204
an integrated study of human and animal infectious disease in the lake victoria crescent small-holder crop-livestock production system, kenya.the neglected zoonotic diseases (nzd) are an understudied group that are a major cause of illness throughout the developing world. in general, little is known about the prevalence and burden of nzds in affected communities, particularly in relation to other infectious diseases with which they are often co-endemic. we describe the design and descriptive epidemiological outputs from an integrated study of human and animal zoonotic and non-zoonotic disease in a rural farming community in western ke ...201728666412
recognition of plasmodium falciparum mature gametocyte-infected erythrocytes by antibodies of semi-immune adults and malaria-exposed children from gabon.transmission of malaria from man to mosquito depends on the presence of gametocytes, the sexual stage of plasmodium parasites in the infected host. naturally acquired antibodies against gametocytes exist and may play a role in controlling transmission by limiting the gametocyte development in the circulation or by interrupting gamete development and fertilization in the mosquito following ingestion. so far, most studies on antibody responses to sexual stage antigens have focused on a subset of g ...201728446190
high prevalence of plasmodium falciparum and soil-transmitted helminth co-infections in a periurban community in kwara state, nigeria.prevalence of malaria and soil-transmitted helminth infections, and the burden of disease are enormous in sub-saharan africa. co-infections aggravate the clinical outcome, but are common due to an overlap of endemic areas. a cross-sectional survey was conducted to assess prevalence, intensity of infection and association between malaria and soil-transmitted helminth infections in a typical periurban community in kwara state. fresh blood and faecal samples were examined using thick blood film and ...201728442321
high-resolution melting pcr assay, applicable for diagnostics and screening studies, allowing detection and differentiation of several babesia spp. infecting humans and animals.the goal of the study was to design a single tube pcr test for detection and differentiation of babesia species in dna samples obtained from diverse biological materials. a multiplex, single tube pcr test was designed for amplification of approximately 400 bp region of the babesia 18s rrna gene. universal primers were designed to match dna of multiple babesia spp. and to have low levels of similarity to dna sequences of other intracellular protozoa and babesia hosts. the pcr products amplified f ...201728795223
development of a novel virus-like particle vaccine platform that mimics the immature form of alphavirus.virus-like particles (vlps) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. here, we developed a novel vlp-based vaccine platform utilizing vlps from the chikungunya virus. we identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising vlp structure. our vlp displays 480 copious copies of an inserted antigen on the vlp surface in a highly symme ...201728515133
a novel lipoate attachment enzyme is shared by plasmodium and chlamydia species.lipoate is an essential cofactor for enzymes that are important for central metabolism and other processes. in malaria parasites, scavenged lipoate from the human host is required for survival. the plasmodium falciparum mitochondrion contains two enzymes (pflipl1 and pflipl2) that are responsible for activating mitochondrial proteins through the covalent attachment of lipoate (lipoylation). lipoylation occurs via a novel redox-gated mechanism that remains poorly understood. we show that pflipl1 ...201728836704
the end of a dogma: the safety of doxycycline use in young children for malaria treatment.anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from southeast asia to africa. furthermore, the recent emergence of resistance to artemisinin-based combination therapy (act) in southeast asia highlights the need to identify new anti-malarial drugs. doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when act is unavailable or when the treatment of severe malaria ...201728407772
measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels.serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. analysis methods have predominantly maintained a single diseas ...201728542223
the novel role of pyrvinium in cancer therapy.pyrvinium pamoate (pp) is a quinoline-derived cyanine dye which was officially approved by fda for its anthelmintic properties and therapeutic function against animal-like protists such as cryptosporidium parvum and plasmodium falciparum in the 1950s. in the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and ...201728500633
structurally linked dynamics in lactate dehydrogenases of evolutionarily distinct species.we present new findings about how primary and secondary structure affects the role of fast protein motions in the reaction coordinates of enzymatic reactions. using transition path sampling and committor distribution analysis, we examined the difference in the role of these fast protein motions in the reaction coordinate of lactate dehydrogenases (ldhs) of apicomplexa organisms plasmodium falciparum and cryptosporidium parvum. having evolved separately from a common malate dehydrogenase ancestor ...201728445027
survey of malaria and anti-dengue virus igg among febrile hiv-infected patients attending a tertiary hospital in abuja, nigeria.dengue and malaria are infections, of great public health concern, especially in sub-saharan africa where the burden of hiv infection is high. this study was conducted to determine the seroprevalence of dengue virus igg antibodies and dengue/malaria coinfection among febrile hiv-infected patients attending the university of abuja teaching hospital, gwagwalada, abuja.201728721101
mosquitoes on a plane: disinsection will not stop the spread of vector-borne pathogens, a simulation study.mosquito-borne diseases are increasingly being recognized as global threats, with increased air travel accelerating their occurrence in travelers and their spread to new locations. since the early days of aviation, concern over the possible transportation of infected mosquitoes has led to recommendations to disinsect aircraft. despite rare reports of mosquitoes, most likely transported on aircraft, infecting people far from endemics areas, it is unclear how important the role of incidentally tra ...201728672006
mosquito-borne diseases in assam, north-east india: current status and key challenges.mosquito-borne diseases, including malaria, japanese encephalitis (je), lymphatic filariasis and dengue, are major public health concerns in the north-eastern state of assam, deterring equitable socioeconomic and industrial development. among these, malaria and je are the predominant infections and are spread across the state. the incidence of malaria is, however, gradually receding, with a consistent decline in cases over the past few years, although entry and spread of artemisinin-resistant pl ...201728607271
immunodominance of adenovirus-derived cd8(+) t cell epitopes interferes with the induction of transgene-specific immunity in adenovirus-based immunization.adenovirus (ad)-based immunization is a popular approach in vaccine development, and ad-based vectors are renowned for their potential to induce strong cd8(+) t cell responses to the encoded transgene. surprisingly, we found before in the mouse friend retrovirus (fv) model that ad-based immunization did not induce cd8(+) t cell responses to the fv leader-gag-derived immunodominant epitope gagl85-93 we show now that induction of gagl85-93-specific cd8(+) t cells was highly effective when leader-g ...201728768877
two cap residues in the s1 subsite of a plasmodium falciparum m1-family aminopeptidase promote broad specificity and enhance catalysis.the aminopeptidase pfa-m1 is a key contributor to peptide catabolism in the human malaria parasite plasmodium falciparum. pfa-m1 substrate specificity is shaped by the cylindrical s1 subsite, which accommodates the sidechain of the substrate p1 residue. at the top of the s1 subsite are two "cap" residues, e572 and m1034, that are positioned to influence s1 subsite specificity. in this study, we have mutated the cap residues, individually and together, and have evaluated the effects on pfa-m1 spe ...201728811124
new adenovirus-based vaccine vectors targeting pfs25 elicit antibodies that inhibit plasmodium falciparum transmission.an effective malaria transmission-blocking vaccine (tbv) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. antibodies against plasmodium falciparum surface protein, pfs25, are known to block parasite development in the mosquito vector. however, in initial clinical trials the limited immunogenicity of recombinant pfs25 protein-in-adjuvant vaccines has been a challenge.201728619071
deeper insight into the six-step domino reaction of aldehydes with malononitrile and evaluation of antiviral and antimalarial activities of the obtained bicyclic products.the straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. an unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehy ...201728638769
malaria, epstein-barr virus infection and the pathogenesis of burkitt's lymphoma.a geographical and causal connection has long been recognized between malaria, epstein-barr virus (ebv) infection and burkitt's lymphoma (bl), but the underlying mechanisms remain obscure. potential clues are that the malaria parasite plasmodium falciparum selectively absorbs vitamin a from the host and depends on it for its biological activities; secondly, alterations in vitamin a (retinoid) metabolism have been implicated in many forms of cancer, including bl. the first author has proposed tha ...201728707393
human and epstein-barr virus mirna profiling as predictive biomarkers for endemic burkitt lymphoma.endemic burkitt lymphoma (ebl) is an aggressive b cell lymphoma and is associated with epstein-barr virus (ebv) and plasmodium falciparum malaria co-infections. central to bl oncogenesis is the over-expression of the myc proto-oncogene which is caused by a translocation of an ig enhancer in approximation to the myc gene. while whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microrna (mirna) dysregulation and differential ...201728400759
decrease in numbers of naive and resting b cells in hiv-infected kenyan adults leads to a proportional increase in total and plasmodium falciparum-specific atypical memory b cells.human immunodeficiency virus type 1 (hiv-1) infection is associated with b cell activation and exhaustion, and hypergammaglobulinemia. how these changes influence b cell responses to coinfections such as malaria is poorly understood. to address this, we compared b cell phenotypes and abs specific for the plasmodium falciparum vaccine candidate apical membrane ag-1 (ama1) in hiv-infected and uninfected adults living in kenya. surprisingly, hiv-1 infection was not associated with a difference in s ...201728526680
expression, purification and characterization of gmz2'.10c, a complex disulphide-bonded fusion protein vaccine candidate against the asexual and sexual life-stages of the malaria-causing plasmodium falciparum parasite.production and characterization of a chimeric fusion protein (gmz2'.10c) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (glurp), merozoite surface protein 3 (msp3), and the highly disulphide bonded pfs48/45 (10c). gmz2'.10c is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite.201728646324
construct design, production, and characterization of plasmodium falciparum 48/45 r0.6c subunit protein produced in lactococcus lactis as candidate vaccine.the sexual stages of plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. the cysteine-rich pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission. however, clinical pfs48/45 sub-unit vaccine development has been hampered by the inability to produce high yields of recombinant protein as the native structure is required for the induction of functional transm ...201728569168
morita-baylis-hillman adducts display anti-inflammatory effects by modulating inflammatory mediator expression in raw264.7 cells.inflammatory response plays an important role not only in the normal physiology but also in pathologies such as cancers. the morita-baylis-hillman adducts (mbha) are a novel group of synthetic molecules that have demonstrated many biological activities against some parasitic cells such as plasmodium falciparum, leishmania amazonensis, and leishmania chagasi, and antimitotic activity against sea urchin embryonic cells was also related. however, little is known about the mechanisms induced by mbha ...201728785138
effect of piplartine and cinnamides on leishmania amazonensis, plasmodium falciparum and on peritoneal cells of swiss mice.plants of the piperaceae family produce piplartine that was used to synthesize the cinnamides.201728415906
alkaloid constituents of the amaryllidaceae plant amaryllis belladonna l.the plant family amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. its representative, amaryllis belladonna, has a geographical distribution covering mainly southern africa, where it has significant usage in the traditional medicine of the native people. in this study, a. belladonna samples collected in brazil were examined for alkaloid content. alkaloid profiles of a. belladonna bulbs were generated by a combination of chroma ...201728858260
lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles.a library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive sar evaluation. four compounds showed an ic50 between 0.25 and 3μm against leishmania donovani and low cytotoxicity. compound g{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an ic50 similar to the reference drug miltefos ...201728789893
bifurcatriol, a new antiprotozoal acyclic diterpene from the brown alga bifurcaria bifurcata.linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. this study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the irish brown alga bifurcariabifurcata. the gross structure of this new natural product was elucidated based on its spectroscopic data (ir, 1d and 2d-nmr, hrms). its absolute configuration was identified by experimental and computational vibrational circular dichroism (vcd) spec ...201728767061
alkamides from anacyclus pyrethrum l. and their in vitro antiprotozoal activity.in our ongoing study to evaluate the antiprotozoal activity of alkamides from asteraceae, a dichloromethane extract from the roots of anacycluspyrethrum l. showed a moderate in vitro activity against the nf54 strain of plasmodium falciparum and against leishmaniadonovani (amastigotes, mhom/et/67/l82 strain). seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. the alkamides were identifi ...201728498323
antiparasitic sesquiterpenes from the cameroonian spice scleria striatinux and preliminary in vitro and in silico dmpk assessment.the antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (dmpk) assessment of six isomeric sesquiterpenes (1-6), isolated from the cameroonian spice scleria striatinux de wild (cyperaceae) is reported. the study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on plasmodium falciparum, trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the in silico method em ...201728421410
anti-trypanosomatid elemanolide sesquiterpene lactones from vernonia lasiopus o. hoffm.sleeping sickness or human african trypanosomiasis (hat) is a neglected tropical disease (ntd) threatening millions of peoples' lives with thousands infected. the disease is endemic in poorly developed regions of sub-saharan africa and is caused by the kinetoplastid "protozoan" parasite trypanosoma brucei. the parasites are transmitted to humans through bites of infected tsetse flies of the genus glossina. the few available drugs for treatment of this disease are highly toxic, difficult to admin ...201728397756
structural characterization of acidic m17 leucine aminopeptidases from the tritryps and evaluation of their role in nutrient starvation in trypanosoma brucei.leucine aminopeptidase (lap) is found in all kingdoms of life and catalyzes the metal-dependent hydrolysis of the n-terminal amino acid residue of peptide or amino acyl substrates. laps have been shown to participate in the n-terminal processing of certain proteins in mammalian cells and in homologous recombination and transcription regulation in bacteria, while in parasites, they are involved in host cell invasion and provision of essential amino acids for growth. the enzyme is essential for su ...201728815215
central and peripheral nervous system disorders following ivermectin mass administration: a descriptive study based on the democratic republic of congo pharmacovigilance system.the mainstay of onchocerciasis control currently is mass administration of ivermectin; however, this may be associated with serious adverse events, including deaths, when administered in areas where onchocerciasis and loiasis are co-endemic.201728600751
antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes.isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. three heterobimetallic complexes were also synthesized from the schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. all complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. against mycobacterium tuberculosis h37rv, the platinum group metal complexes showed glycerol- ...201728713884
insights into integrated lead generation and target identification in malaria and tuberculosis drug discovery.new, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. however, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. ...201728636311
engineering and purification of a thermostable, high-yield, variant of pfcrt, the plasmodium falciparum chloroquine resistance transporter.historically chloroquine was used to treat the most deadly form of malaria, caused by the parasite plasmodium falciparum. the selective pressure of chloroquine therapy led to the rapid emergence of chloroquine resistant parasites. resistance has been attributed to the plasmodium falciparum chloroquine resistance transporter (pfcrt), an integral membrane protein of unknown structure. a pfcrt structure would provide new insights into how the protein confers chloroquine resistance and thereby also ...201728823509
the rxlr motif of the host targeting effector avr3a of phytophthora infestans is cleaved before secretion.when plant-pathogenic oomycetes infect their hosts, they employ a large arsenal of effector proteins to establish a successful infection. some effector proteins are secreted and are destined to be translocated and function inside host cells. the largest group of translocated proteins from oomycetes is the rxlr effectors, defined by their conserved n-terminal arg-xaa-leu-arg (rxlr) motif. however, the precise role of this motif in the host cell translocation process is unclear. here, detailed bio ...201728522546
perillyl alcohol exhibits in vitro inhibitory activity against plasmodium falciparum and protects against experimental cerebral malaria.the development of new drugs is one of the strategies to control malaria. isoprenoid biosynthesis in plasmodium falciparum is an essential pathway for parasite survival, and therefore a potential target for new antimalarial drugs. indeed, plant-derived secondary metabolites such as terpenes exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in p. falciparum. in this study, the in vitro antiplasmodial activity of perillyl alcohol (poh) was evaluated, along with its in vi ...201728843818
down-regulation of tim-3 in monocytes and macrophages in plasmodium infection and its association with parasite clearance.t-cell immunoglobulin and mucin-domain-containing molecule 3 (tim-3) has complicated roles in regulating monocytes and macrophages in various diseases and it tends to be an inhibitory molecule to facilitate the immune escape of parasites in malaria. however, the mechanisms of tim-3 mediated responses in monocytes and macrophages in malaria have not been clear. in this study, we found that plasmodium infection down-regulated tim-3 expression in peripheral monocytes of patients suffering from plas ...201728824565
hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity.antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. here, we report the identification and characterization of hexahydroquinolines (hhqs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite plasmodium falciparum. this activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and re ...201728808258
antimalarial evaluation of selected medicinal plant extracts used in iranian traditional medicine.in an attempt to discover new natural active extracts against malaria parasites, the present study evaluated the antiplasmodial properties of selected plants based on iranian traditional medicine.201728804611
antiplasmodial activity and cytotoxicity of ethanol extract of zea mays root.zea mays root decoction that has been traditionally used for the treatment of malaria by various tribes in nigeria, was evaluated for antimalarial potential against malaria parasites using in vivo and in vitro models.201728748174
plasmodium berghei p47 is essential for ookinete protection from the anopheles gambiae complement-like response.malaria is a mosquito-borne disease affecting millions of people every year. the rodent parasite plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. the 6-cysteine protein p47, known to be important for p. berghei female gamete fertility, is shown to serve a different function in plasmodium falciparum, protecting ookinetes from the mosquito immune response. here, we investigate the ...201728729672
[fe-s] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite.the relict plastid (apicoplast) of the malaria parasite is the site for important biochemical pathways and is essential for parasite survival. the sulfur mobilization (suf) pathway of iron-sulfur [fe-s] cluster assembly in the apicoplast of plasmodium spp. is of interest due to its absence in the human host suggesting the possibility of antimalarial intervention through apicoplast [fe-s] biogenesis. we report biochemical characterization of components of the plasmodium falciparum apicoplast suf ...201728695709
an exported protein-interacting complex involved in the trafficking of virulence determinants in plasmodium-infected erythrocytes.the malaria parasite, plasmodium falciparum, displays the p. falciparum erythrocyte membrane protein 1 (pfemp1) on the surface of infected red blood cells (rbcs). we here examine the physical organization of pfemp1 trafficking intermediates in infected rbcs and determine interacting partners using an epitope-tagged minimal construct (pfemp1b). we show that parasitophorous vacuole (pv)-located pfemp1b interacts with components of the ptex (plasmodium translocon of exported proteins) as well as a ...201728691708
host-mediated impairment of parasite maturation during blood-stage plasmodium infection.severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to plasmodium falciparum nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. we used a unique in vivo approach to determine the fate of a single coho ...201728673996
efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model.the emergence of multidrug-resistant strains of plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. the study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed ' ...201728673299
examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy.malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. because of widespread resistance to conventional antimalarials, including chloroquine (cq), new drugs are urgently needed. here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. in vitro efficacy was evaluated by a lactate dehydrogenase (l ...201728668677
3-hydroxy-n'-arylidenepropanehydrazonamides with halo-substituted phenanthrene scaffolds cure p. berghei infected mice when administered perorally.structural optimization of 3-hydroxy-n'-arylidenepropanehydrazonamides provided new analogs with nanomolar to subnanomolar antiplasmodial activity against asexual blood stages of plasmodium falciparum, excellent parasite selectivity, and nanomolar activity against the earliest forms of gametocyte development. particularly, derivatives with a 1,3-dihalo-6-trifluoromethylphenanthrene moiety showed outstanding in vivo properties and demonstrated in part curative activity in the plasmodium berghei m ...201728653845
suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase.aspartate, which is converted from oxaloacetate (oaa) by aspartate aminotransferase, is considered an important precursor for purine salvage and pyrimidine de novo biosynthesis, and is thus indispensable for the growth of plasmodium parasites at the asexual blood stages. oaa can be produced in malaria parasites via two routes: (i) from phosphoenolpyruvate (pep) by phosphoenolpyruvate carboxylase (pepc) in the cytosol, or (ii) from fumarate by consecutive reactions catalyzed by fumarate hydratase ...201728606087
menoctone resistance in malaria parasites is conferred by m133i mutations in cytochrome b that are transmissible through mosquitoes.malaria-related mortality has slowly decreased over the past decade; however, eradication of malaria requires the development of new antimalarial chemotherapies that target liver stages of the parasite and combat the emergence of drug resistance. the diminishing arsenal of anti-liver-stage compounds sparked our interest in reviving the old and previously abandoned compound menoctone. in support of these studies, we developed a new convergent synthesis method that was facile, required fewer steps ...201728584157
the fibrinogen-like domain of frep1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen.frep1 in mosquito midguts facilitates plasmodium falciparum parasite transmission. the fibrinogen-like (fbg) domain of frep1 is highly conserved (>90% identical) among anopheles species from different continents, suggesting that anti-fbg antibodies may block malaria transmission to all anopheline mosquitoes. using standard membrane-feeding assays, anti-frep1 polyclonal antibodies significantly blocked transmission of plasmodium berghei and plasmodium vivax to anopheles gambiae and anopheles diru ...201728533429
anti-plasmodial assessment of four different iranian propolis extracts.eradication of malaria will depend on discovery of new intervention tools such as anti-malarial drugs. due to the increasing interest in the application of propolis against significant clinical pathogenic agents, the aim of the present investigation was to evaluate the anti-plasmodial effect of iranian propolis extracts against chloroquine (cq)-sensitive plasmodium falciparum 3d7 and plasmodium berghei (anka strain).201728510462
identification of protective b-cell epitopes within the novel malaria vaccine candidate plasmodium falciparum schizont egress antigen 1.naturally acquired antibodies to plasmodium falciparum schizont egress antigen 1 (pfsea-1a) are associated with protection against severe malaria in children. vaccination of mice with sea-1a from plasmodium berghei (pbsea-1a) decreases parasitemia and prolongs survival following p. berghei anka challenge. to enhance the immunogenicity of pfsea-1a, we identified five linear b-cell epitopes using peptide microarrays probed with antisera from nonhuman primates vaccinated with recombinant pfsea-1a ( ...201728468980
icam-1 is a key receptor mediating cytoadherence and pathology in the plasmodium chabaudi malaria model.parasite cytoadherence within the microvasculature of tissues and organs of infected individuals is implicated in the pathogenesis of several malaria syndromes. multiple host receptors may mediate sequestration. the identity of the host receptor(s), or the parasite ligand(s) responsible for sequestration of plasmodium species other than plasmodium falciparum is largely unknown. the rodent malaria parasites may be useful to model interactions of parasite species, which lack the var genes with the ...201728468674
antimalarial efficacy of mmv390048, an inhibitor of plasmodium phosphatidylinositol 4-kinase.as part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. stemming from this series, we found that the derivative, mmv390048, lacked cross-resistance with current drugs used to treat malaria. this compound was efficacious against all plasmodium life cycle stages, apart from late hypnozoites in the liver. efficacy was shown in the humanized plasmodium fa ...201728446690
variation in species composition and infection rates of anopheles mosquitoes at different altitudinal transects, and the risk of malaria in the highland of dirashe woreda, south ethiopia.the transmission of malaria is heterogeneous, and varies due to altitude. the information on whether the transmission of malaria is indigenous or imported to highland areas is scarce. therefore, this study aimed to assess the species composition and infection rates of anopheles at different altitudinal transects, and the risk of malaria if any in the highland of dirashe woreda, south ethiopia.201728724450
identification and characterization of the antiplasmodial activity of hsp90 inhibitors.the recent reduction in mortality due to malaria is being threatened by the appearance of plasmodium falciparum parasites that are resistant to artemisinin in southeast asia. to limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. towards that end, the antiplasmodial potential of several hsp90 inhibitors was c ...201728724415
a dual colour fluorescence in situ hybridization (fish) assay for identifying the zoonotic malaria parasite plasmodium knowlesi with a potential application for the specific diagnosis of knowlesi malaria in peripheral-level laboratories of southeast asia.plasmodium knowlesi is primarily responsible for zoonotic malaria in several southeast asian countries. precise identification of the parasite in the blood of patients presently relies on an expensive and elaborate pcr procedure because microscopic examination of blood and other available field identification techniques lack adequate specificity. therefore, the use of a simple and inexpensive dual-colour fluorescence in situ hybridization (fish) assay, analogous to fish assays recently described ...201728724402
novel plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. our limited understanding of plasmodium biology hinders the elucidation of resistance mechanisms. in this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms.201728724354
artemisinin-resistant plasmodium falciparum in africa. 201728723328
artemisinin-resistant plasmodium falciparum in africa. 201728723327
estimating the added utility of highly sensitive histidine-rich protein 2 detection in outpatient clinics in sub-saharan africa.most malaria testing is by rapid diagnostic tests (rdts) that detect plasmodium falciparum histidine-rich protein 2 (hrp2). recently, several rdt manufacturers have developed highly sensitive rdts (hsrdts), promising a limit of detection (lod) orders of magnitude lower than conventional rdts. to model the added utility of hsrdts, hrp2 concentration in angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. the distribution of hrp2 concentration was bimodal in bo ...201728722629
respiratory complications of plasmodium vivax malaria: systematic review and meta-analysis.malaria, a major global public health problem, is mainly caused by plasmodium falciparum and plasmodium vivax, and is responsible for nearly half a million deaths annually. although p. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. however, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. a systematic search for articles reporting respiratory complications ...201728722625
phase 2a, open-label, 4-escalating-dose, randomized multicenter study evaluating the safety and activity of ferroquine (ssr97193) plus artesunate, versus amodiaquine plus artesunate, in african adult men with uncomplicated plasmodium falciparum malaria.artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated plasmodium falciparum malaria. ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (as). we did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three african hospitals: two gabonese and one kenyan. we recruited adult men with symptomatic uncomplicated p. falciparum monoinfectio ...201728722611
optimizing direct membrane and direct skin feeding assays for plasmodium falciparum transmission-blocking vaccine trials in bancoumana, mali.malaria transmission-blocking vaccines (tbv) have been evaluated in field trials in mali, since 2013. however, the assays currently used to measure serum antibody tb activity (tba) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. herein, we report a study conducted in bancoumana village, mali, where we identify and optimize the parameters that contribute to successful mosquito feed ...201728722588
lack of geospatial population structure yet significant linkage disequilibrium in the reservoir of plasmodium falciparum in bongo district, ghana.malaria control in west africa is impeded by the large reservoir of chronic asymptomatic plasmodium falciparum infections in the human population. this study aimed to assess the extent of diversity in the p. falciparum reservoir in bongo district (bd), ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. analysis of the variation in 12 microsatellite loci was completed for 200 p. falciparum isolates collected from a cross-sectional survey of ...201728722587
a direct from blood reverse transcriptase polymerase chain reaction assay for monitoring falciparum malaria parasite transmission in elimination settings.we describe a novel one-step reverse transcriptase real-time pcr (direct rt-pcr) for plasmodium falciparum malaria parasites that amplifies rna targets directly from blood. we developed the assay to identify gametocyte-specific transcripts in parasites from patient blood samples, as a means of monitoring malaria parasite transmission in field settings. to perform the test, blood is added directly to a master mix in pcr tubes and analyzed by real-time pcr. the limit of detection of the assay on b ...201728722583
high iron levels are associated with increased malaria risk in infants during the first year of life in benin.the world health organization (who) estimates that 40% of children in low-income countries are anemic. therefore, iron supplements are recommended by who in areas with high anemia rates. however, some studies have set into question the benefits of iron supplementation in malaria-endemic regions. in benin, a west african country with high prevalence of anemia and malaria, no iron supplements are given systematically to infants so far despite the who recommendations. in this context, we wanted to ...201728722565
exploring anti-malarial potential of fda approved drugs: an in silico approach.the critically important issue on emergence of drug-resistant malarial parasites is compounded by cross resistance, where resistance to one drug confers resistance to other chemically similar drugs or those that share mode of action. this aspect requires discovery of new anti-malarial compounds or formulation of new combination therapy. the current study attempts to contribute towards accelerating anti-malarial drug development efforts, by exploring the potential of existing fda-approved drugs t ...201728720135
in vitro antioxidant and antimalarial activities of leaves, pods and bark extracts of acacia nilotica (l.) del.the emergence of drug resistant malaria is threatening our ability to treat and control malaria in the southeast asian region. there is an urgent need to develop novel and chemically diverse antimalarial drugs. this study aimed at evaluating the antimalarial and antioxidant potentials of acacia nilotica plant extracts.201728720134
effect of seasonal malaria chemoprevention on the acquisition of antibodies to plasmodium falciparum antigens in ouelessebougou, mali.seasonal malaria chemoprevention (smc) is a new strategy to reduce malaria burden in young children in sahelian countries. it consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. however, it is not clear if there is a cumulative effect of smc over time on acquisition of antibodies to malaria antigens.201728720100
malaria-related hospitalizations in the united states, 2000-2014.few data are available on the burden of malaria hospitalization in the united states. study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. u.s. malaria cases identified from hospitalization discharge records in the 2000-2014 nationwide inpatient sample were examined. frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and d ...201728719326
molecular epidemiology of malaria in cameroon and côte d'ivoire. xxxi. kelch 13 propeller sequences in plasmodium falciparum isolates before and after implementation of artemisinin-based combination therapy.artemisinin-resistant malaria has not been reported from africa, but resistance can possibly spread from asia or arise independently in africa. the emergence of artemisinin resistance in africa can be monitored by molecular assay of kelch 13 (k13) propeller sequences. a total of 251 archived dna samples of plasmodium falciparum isolates collected in 2002, 2003, and 2006 in yaounde, cameroon, and 47 samples collected in 2006 and 2013 in abidjan, côte d'ivoire, were analyzed for k13-propeller sequ ...201728719312
seasonal variation in the epidemiology of asymptomatic plasmodium falciparum infections across two catchment areas in bongo district, ghana.understanding the epidemiology of asymptomatic plasmodium falciparum infections is critical for countries to move toward malaria elimination. using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in bongo district, ghana. asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (p < 0.001). using the 1 ...201728719306
molecular markers for sensitive detection of plasmodium falciparum asexual stage parasites and their application in a malaria clinical trial.plasmodium falciparum parasite life stages respond differently to antimalarial drugs. sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. in this study, we compared the performance of skeleton-binding protein 1 (sbp1), ring-infected erythrocyte surface antigen, hyp8, ring-exported protein 1 (rex1), and phistb mrna for detecting ring-stage trophozoite-specific t ...201728719294
symptomatic falciparum malaria after living in a nonendemic area for 10 years: recrudescence or indigenous transmission?abstractwe report the case of a patient from mali who, after 10 years of living in spain, presented with symptomatic plasmodium falciparum malaria without having visited an endemic area during that time. we cannot completely rule out the possibility of indigenous transmission, but this case most likely represents recrudescence of an infection acquired over 10 years earlier.201728719260
heterologous expression, purification, and functional analysis of plasmodium falciparum phosphatidylinositol 3'-kinase.the plasmodium falciparum malarial parasite genome appears to encode one and only one phosphatidylinositol 3'-kinase (pi3k), and sequence analysis suggests that the enzyme is a "class iii"- or "vps34"-type pi3k. pfvps34 has generated excitement as a possible druggable target and potentially a key target of artemisinin-based antimalarials. in this study, we optimize the pfvps34 gene for heterologous expression in yeast, purify the protein to homogeneity, use a recently validated quantitative assa ...201728719180
development of an immunosensor for pfhrp 2 as a biomarker for malaria detection.plasmodium falciparum histidine-rich protein 2 (pfhrp 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. an enzyme-linked immunosorbent assay (elisa) was first developed to evaluate the immunoreagent's suitability for the sensor's development. a gold-based sensor with an integrated counter and an ag/agcl reference electrode was first selected and characterised and then used to develop the immunosensor for pfhrp 2, which enables a low cost, easy to use, and ...201728718841
an analytical approach to reduce between-plate variation in multiplex assays that measure antibodies to plasmodium falciparum antigens.antibodies play an important role in immunity to malaria. recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized.201728716094
dynamics in multiplicity of plasmodium falciparum infection among children with asymptomatic malaria in central ghana.the determinants of malaria parasite virulence is not entirely known, but the outcome of malaria infection (asymptomatic or symptomatic) has been associated with carriage of distinct parasite genotypes. alleles considered important for erythrocyte invasion and selected as candidate targets for malaria vaccine development are increasingly being shown to have distinct characteristics in infection outcomes. any unique/distinct patterns or alleles linked to infection outcome should be reproducible f ...201728716086
multiplexing detection of igg against plasmodium falciparum pregnancy-specific antigens.pregnant women exposed to plasmodium falciparum generate antibodies against var2csa, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. there is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. here we aimed at developing a multiplex-immunoassay to detect antibodies against var2csa antigens.201728715465
antiplasmodial prenylated flavanonols from tephrosia subtriflora.the ch2cl2/meoh (1:1) extract of the aerial parts of tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone b, and the known flavanonols ms-ii (2) and mundulinol. the structures were elucidated by the use of nmr spectroscopy and mass spectrometry. the absolute configuration of the flavanonols was determined based on quantum chemical ecd calculations. in the antiplasmodial assay, compound 2 showed the highest activity against chl ...201728714338
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