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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
relationship between antibody levels, igg binding to plasmodium falciparum-infected erythrocytes, and disease outcome in hospitalized urban malaria patients from dakar, sénégal.background. management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. protection is partly based on igg responses to parasite antigens exposed at the surface of infected erythrocytes (irbcs). these igg responses appeared low during clinical infection, particularly in severe disease. methods. we analyzed the igg binding capacity to the surface of live erythrocytes infected by knob positive fcr3 strain. sera from 69 c ...201627563669
multiplicity of infection and genetic diversity of plasmodium falciparum isolates from patients with uncomplicated and severe malaria in gezira state, sudan.multiplicity and genetic diversity of plasmodium falciparum infection might play a role in determining the clinical outcome of malaria infection and could be a fair reflection of the disease transmission rate. this study investigated the genetic diversity of p. falciparum and multiplicity of infection in relation to the severity of malaria and age of patients in gezira state, sudan.201627350250
analysis of asymptomatic and clinical malaria in urban and suburban settings of southwestern ethiopia in the context of sustaining malaria control and approaching elimination.malaria intervention in ethiopia has been strengthened significantly in the past decade. the ethiopian government recently stratified the country based upon annual parasite incidence into malaria free, low, moderate and high transmission strata. districts with low transmission were targeted for indigenous transmission elimination. surveillance on malaria disease incidence is needed for planning control and elimination efforts.201627129785
identification of different malaria patterns due to plasmodium falciparum and plasmodium vivax in ethiopian children: a prospective cohort study.the identification of epidemiological pattern of infection with plasmodium falciparum and plasmodium vivax in malaria-endemic area, where multiple episodes are common, is important for intervention programmes.201627075667
widespread distribution of plasmodium vivax malaria in mauritania on the interface of the maghreb and west africa.plasmodium vivax is very rarely seen in west africa, although specific detection methods are not widely applied in the region, and it is now considered to be absent from north africa. however, this parasite species has recently been reported to account for most malaria cases in nouakchott, the capital of mauritania, which is a large country at the interface of sub-saharan west africa and the maghreb region in northwest africa.201626861780
disrupting mosquito reproduction and parasite development for malaria control.the control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. in light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. here, we show that compounds targ ...201627977810
efficacy and safety of high-dose ivermectin for reducing malaria transmission (ivermal): protocol for a double-blind, randomized, placebo-controlled, dose-finding trial in western kenya.innovative approaches are needed to complement existing tools for malaria elimination. ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150 to 200 mcg/kg. it also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. however, the effect after a 150 to 200 mcg/kg oral dose is short-lived (6 to 11 days). modeling suggests higher doses, which prolong the mosquitoci ...201627856406
comparison of molecular quantification of plasmodium falciparum gametocytes by pfs25 qrt-pcr and qt-nasba in relation to mosquito infectivity.quantifying gametocyte densities in natural malaria infections is important to estimate malaria transmission potential. two molecular methods (pfs25 mrna quantitative reverse transcriptase pcr (qrt-pcr) and pfs25 mrna quantitative nucleic acid sequence based amplification (qt-nasba)) are commonly used to determine gametocyte densities in clinical and epidemiological studies and allow gametocyte detection at densities below the microscopic threshold for detection. here, reproducibility of these m ...201627821171
serological markers to measure recent changes in malaria at population level in cambodia.serological markers for exposure to different plasmodium species have recently been used in multiplex immunoassays based on the luminex technology. however, interpretation of the assay results requires consideration of the half-life of specific antibodies against these markers. therefore, the aim of the present study was to document the half-life of malaria specific serological makers, as well as assessing the sensitivity of these markers to pick up recent changes in malaria exposure.201627809852
phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant pichia pastoris-expressed plasmodium falciparum apical membrane antigen 1 (pfama1-fvo [25-545]) in healthy malian adults in bandiagara.the safety and immunogenicity of pfama1, adjuvanted with alhydrogel(®) was assessed in malaria-experienced malian adults. the malaria vaccine, pfama1-fvo [25-545] is a recombinant protein pichia pastoris-expressed ama-1 from plasmodium falciparum fvo clone adsorbed to alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin.201627577237
adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated plasmodium falciparum malaria in tanzania: a randomized, single-blinded clinical trial.the world health organization (who) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (pq) to artemisinin-based combination therapy (act) in low transmission settings as a component of pre-elimination or elimination programmes. however, it is unclear whether that influences the act cure rate. the study assessed treatment outcome of artemether-lumefantrine (al) plus a single pq dose (0.25 mg/kg) versus standard al regimen for treatment of acute uncompli ...201627565897
selection of n86f184d1246 haplotype of pfmrd1 gene by artemether-lumefantrine drug pressure on plasmodium falciparum populations in senegal.the use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in southeast asia. monitoring of artemisinin combination therapy (act) is critical in order to detect and prevent the spread of resistance in endemic areas. ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. one gene that has been associated in some act partner drug resistance is the plasmodium falciparum multidrug resistance ...201627562216
malaria intervention scale-up in africa: effectiveness predictions for health programme planning tools, based on dynamic transmission modelling.scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the spectrum health programme planning tool.201627538889
improvement in protein domain identification is reached by breaking consensus, with the agreement of many profiles and domain co-occurrence.traditional protein annotation methods describe known domains with probabilistic models representing consensus among homologous domain sequences. however, when relevant signals become too weak to be identified by a global consensus, attempts for annotation fail. here we address the fundamental question of domain identification for highly divergent proteins. by using high performance computing, we demonstrate that the limits of state-of-the-art annotation methods can be bypassed. we design a new ...201627472895
safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated plasmodium falciparum malaria in tanzania.this study assessed the safety of the new world health organization (who) recommendation of adding a single low-dose of primaquine (pq) to standard artemisinin-based combination therapy (act), regardless of individual glucose-6-phosphate dehydrogenase (g6pd) status, for treatment of acute uncomplicated plasmodium falciparum malaria in tanzania.201627287612
the roopfs study to assess whether improved housing provides additional protection against clinical malaria over current best practice in the gambia: study protocol for a randomized controlled study and ancillary studies.in malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. this study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (llins) and prompt treatment in the gambia, determine the incremental cost-effectiveness of the interventions, and analyze the housing market in the gambia.201627255167
marked rise in the prevalence of asymptomatic plasmodium falciparum infection in rural gabon.control strategies implemented a decade ago led to a marked reduction in the prevalence of malaria in many countries. in dienga, southeastern gabon, the prevalence of microscopic p. falciparum infection was 7% in 2003, close to the pre-elimination threshold of 5%. the aim of this work was to determine the prevalence of p. falciparum infection in the same community a decade later. a cohort of 370 individuals aged from 3 to 85 years living in dienga was investigated for p. falciparum infection; du ...201627228058
a significant association between deltamethrin resistance, plasmodium falciparum infection and the vgsc-1014s resistance mutation in anopheles gambiae highlights the epidemiological importance of resistance markers.the success of malaria vector control is threatened by widespread pyrethroid insecticide resistance. however, the extent to which insecticide resistance impacts transmission is unclear. the objective of this study was to examine the association between the ddt/pyrethroid knockdown resistance mutation vgsc-1014s, commonly termed kdr, and infection with plasmodium falciparum sporozoites in anopheles gambiae.201627216484
effects of larvicidal and larval nutritional stresses on anopheles gambiae development, survival and competence for plasmodium falciparum.many studies have shown that the environment in which larvae develop can influence adult characteristics with consequences for the transmission of pathogens. we investigated how two environmental stresses (larviciding and nutritional stress) interact to affect anopheles gambiae (previously an. gambiae s molecular form) life history traits and its susceptibility for field isolates of its natural malaria agent plasmodium falciparum.201627107591
the nonartemisinin sesquiterpene lactones parthenin and parthenolide block plasmodium falciparum sexual stage transmission.parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (sql) and one of the most important antimalarial drugs available. parthenin, like artemisinin, has an effect onplasmodiumblood stage development. we extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofplasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic ins ...201626787692
genomes of cryptic chimpanzee plasmodium species reveal key evolutionary events leading to human malaria.african apes harbour at least six plasmodium species of the subgenus laverania, one of which gave rise to human plasmodium falciparum. here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as plasmodium reichenowi and plasmodium gaboni based on the subgenomic fragments. genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. both p. reichenowi and p. gaboni are 10-fold more dive ...201627002652
plasmodium falciparum parasitaemia and clinical malaria among school children living in a high transmission setting in western kenya.malaria among school children is increasingly receiving attention, yet the burden of malaria in this age group is poorly defined. this study presents data on malaria morbidity among school children in bungoma county, western kenya.201626969283
plasmodium falciparum: multifaceted resistance to artemisinins.plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. artemisinin resistance is due to mutation of the pfk13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. the enhanced p. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage an ...201626955948
operational strategies of anti-malarial drug campaigns for malaria elimination in zambia's southern province: a simulation study.malaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. to achieve this goal in southern province, zambia a mass test and treat (mtat) campaign was conducted from 2011-2013 to complement high coverage of long-lasting insecticide-treated nets (llin). to identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operatio ...201626957364
single low dose primaquine to reduce gametocyte carriage and plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial.a single low dose (0.25 mg/kg) of primaquine is recommended as a gametocytocide in combination with artemisinin-based combination therapies for plasmodium falciparum but its effect on post-treatment gametocyte circulation and infectiousness to mosquitoes has not been quantified.201626952094
exposure to deltamethrin affects development of plasmodium falciparum inside wild pyrethroid resistant anopheles gambiae s.s. mosquitoes in uganda.pyrethroid resistance in african vector mosquitoes is a threat to malaria control. resistant mosquitoes can survive insecticide doses that would normally be lethal. we studied effects of such doses on plasmodium falciparum development inside kdr-resistant anopheles gambiae s.s. in uganda.201626911550
variation in susceptibility of african plasmodium falciparum malaria parasites to tep1 mediated killing in anopheles gambiae mosquitoes.anopheles gambiae s.s. mosquitoes are efficient vectors for plasmodium falciparum, although variation exists in their susceptibility to infection. this variation depends partly on the thioester-containing protein 1 (tep1) and tep depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. polymorphism in the plasmodium gene coding for the surface protein pfs47 modulates resistance of some parasite laboratory strains to tep1-mediated killing. here, we e ...201626861587
therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest benin.artemether/lumefantrine (coartem(®)) has been used as a treatment for uncomplicated plasmodium falciparum infection since 2004 in benin. this open-label, non-randomized study evaluated efficacy of artemether-lumefantrine (al) in treatment of uncomplicated falciparum malaria in children aged 6-59 months in two malaria transmission sites in northwest benin.201626801767
lack of k13 mutations in plasmodium falciparum persisting after artemisinin combination therapy treatment of kenyan children.studies in southeast asia reported a strong relationship between polymorphisms at the propeller domain of the kelch 13 (k13) protein encoded by the plasmodium falciparum k13 (pfk13) gene and delayed parasite clearance after artemisinin treatment. in africa, p. falciparum remains susceptible and combination therapy regimens which include an artemisinin component display good efficacy. using quantitative real-time pcr (qpcr), sub-microscopic persistence of p. falciparum has previously been reporte ...201626801909
genetic structure of a local population of the anopheles gambiae complex in burkina faso.members of the anopheles gambiae species complex are primary vectors of human malaria in africa. population heterogeneities for ecological and behavioral attributes expand and stabilize malaria transmission over space and time, and populations may change in response to vector control, urbanization and other factors. there is a need for approaches to comprehensively describe the structure and characteristics of a sympatric local mosquito population, because incomplete knowledge of vector populati ...201626731649
genetic diversity of plasmodium falciparum isolates from uncomplicated malaria cases in ghana over a decade.genotyping malaria parasites to assess their diversity in different geographic settings have become necessary for the selection of antigenic epitopes for vaccine development and for antimalarial drug efficacy or resistance investigations. this study describes the genetic diversity of plasmodium falciparum isolates from uncomplicated malaria cases over a ten year period (2003-2013) in ghana using the polymorphic antigenic marker, merozoite surface protein 2 (msp2).201627460474
lack of artemisinin resistance in plasmodium falciparum in northwest benin after 10 years of use of artemisinin-based combination therapy.in benin, artemisinin-based combination therapy (act) has been recommended as the first-line treatment for uncomplicated plasmodium falciparum malaria since 2004. the emergence in southeast asia of parasites that are resistant to artemisinins poses a serious threat to global control of this disease. the presence of artemisinin resistance genotypes in parasite populations in benin is currently unknown. the present study investigated the prevalence of relevant k13-propeller gene polymorphisms in p ...201627443837
interactive cost of plasmodium infection and insecticide resistance in the malaria vector anopheles gambiae.insecticide resistance raises concerns for the control of vector-borne diseases. however, its impact on parasite transmission could be diverse when considering the ecological interactions between vector and parasite. thus we investigated the fitness cost associated with insecticide resistance and plasmodium falciparum infection as well as their interactive cost on anopheles gambiae survival and fecundity. in absence of infection, we observed a cost on fecundity associated with insecticide resist ...201627432257
spatial effects on the multiplicity of plasmodium falciparum infections.as malaria is being pushed back on many frontiers and global case numbers are declining, accurate measurement and prediction of transmission becomes increasingly difficult. low transmission settings are characterised by high levels of spatial heterogeneity, which stands in stark contrast to the widely used assumption of spatially homogeneous transmission used in mathematical transmission models for malaria. in the present study an individual-based mathematical malaria transmission model that inc ...201627711149
factors associated with high heterogeneity of malaria at fine spatial scale in the western kenyan highlands.the east african highlands are fringe regions between stable and unstable malaria transmission. what factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. in a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes.201627259286
application of serological tools and spatial analysis to investigate malaria transmission dynamics in highland areas of southwest uganda.serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to p. falciparum merozoite surface protein-119 (msp-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. clusters of p. falciparum parasi ...201627022156
the epidemiology of residual plasmodium falciparum malaria transmission and infection burden in an african city with high coverage of multiple vector control measures.in the tanzanian city of dar es salaam, high coverage of long-lasting insecticidal nets (llins), larvicide application (la) and mosquito-proofed housing, was complemented with improved access to artemisinin-based combination therapy and rapid diagnostic tests by the end of 2012.201627216734
an evolutionary approach to identify potentially protective b cell epitopes involved in naturally acquired immunity to malaria and the role of eba-175 in protection amongst denizens of bolifamba, cameroon.the search for a vaccine against malaria caused by plasmodium falciparum has lasted for more than 100 years, with considerable progress in the identification of a number of vaccine candidates. the post-genomic era offers new opportunities for an expedited search using rational vaccine design and prioritization of key b-cell epitopes involved in natural acquired immunity.201627207101
plasmodium falciparum malaria parasitaemia among indigenous batwa and non-indigenous communities of kanungu district, uganda.the indigenous batwa of southwestern uganda are among the most highly impoverished populations in uganda, yet there is negligible research on the prevalence of malaria in this population. plasmodium falciparum malaria parasitaemia prevalence was estimated in an indigenous batwa and a non-indigenous neighbouring population, and an exploration of modifiable risk factors was carried out to identify potential entry points for intervention. additionally, evidence of zooprophylaxis was assessed, hypot ...201627146298
malaria parasitaemia and the use of insecticide-treated nets (ints) for malaria control amongst under-5 year old children in calabar, nigeria.malaria remains a major cause of febrile illness in nigeria and interventions to reduce malaria burden in nigeria focus on the use of insecticide-treated nets. this study determined the prevalence of malaria parasitaemia and the use of insecticide-treated nets (itns) for the control of malaria amongst under-five year old children in calabar, nigeria.201627080122
malaria hotspots defined by clinical malaria, asymptomatic carriage, pcr and vector numbers in a low transmission area on the kenyan coast.targeted malaria control interventions are expected to be cost-effective. clinical, parasitological and serological markers of malaria transmission have been used to detect malaria transmission hotspots, but few studies have examined the relationship between the different potential markers in low transmission areas. the present study reports on the relationships between clinical, parasitological, serological and entomological markers of malaria transmission in an area of low transmission intensi ...201627075879
key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-saharan african countries.as malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. however, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-saharan africa.201627068686
high prevalence of plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern malawi.in endemic areas, many people experience asymptomatic plasmodium infections, particularly older children and adults, but their transmission contribution is unknown. though not the exclusive determinant of infectiousness, transmission from humans to mosquitoes requires blood meals containing gametocytes. gametocytes often occur at submicroscopic densities, challenging measurement in human populations. more sensitive molecular techniques allow better characterization of gametocyte epidemiologic pa ...201627809907
impact of highland topography changes on exposure to malaria vectors and immunity in western kenya.it is almost an axiom that in the african highlands (above 1,500 m) transmission of plasmodium falciparum is limited primarily by low ambient temperature and that small changes in temperature could result in temporary favorable conditions for unstable transmission within populations that have acquired little functional immunity. the pattern of malaria transmission in the highland plateau ecosystems is less distinct due to the flat topography and diffuse hydrology resulting from numerous streams. ...201627790610
a prospective cohort study to assess the micro-epidemiology of plasmodium falciparum clinical malaria in ilha josina machel (manhiça, mozambique).after the decrease in clinical malaria incidence observed in mozambique until 2009, a steady resurgence of cases per year has been reported nationally, reaching alarming levels in 2014. however, little is known about the clinical profile of the cases presented, or the possible epidemiological factors contributing to the resurgence of cases.201627577880
prevalence of crt and mdr-1 mutations in plasmodium falciparum isolates from grande comore island after withdrawal of chloroquine.in comoros, the widespread of chloroquine (cq)-resistant plasmodium falciparum populations was a major obstacle to malaria control, which led to the official withdrawal of cq in 2004. continuous monitoring of cq-resistant markers of the p. falciparum cq resistant transporter (pfcrt) and the p. falciparum multiple drug resistance 1 (pfmdr-1) is necessary inder to obtain first-hand information on cq susceptibility of parasite populations in the field. the objective of this study is to assess the p ...201627527604
tafenoquine and its potential in the treatment and relapse prevention of plasmodium vivax malaria: the evidence to date.despite declining global malaria incidence, the disease continues to be a threat to people living in endemic regions. in 2015, an estimated 214 million new malaria cases and 438,000 deaths due to malaria were recorded. plasmodium vivax is the second most common cause of malaria next to plasmodium falciparum. vivax malaria is prevalent especially in southeast asia and the horn of africa, with enormous challenges in controlling the disease. some of the challenges faced by vivax malaria-endemic cou ...201627528800
high susceptibility of wild anopheles funestus to infection with natural plasmodium falciparum gametocytes using membrane feeding assays.anopheles funestus is a major vector of malaria in sub-saharan africa. however, because it is difficult to colonize, research on this mosquito species has lagged behind other vectors, particularly the understanding of its susceptibility and interactions with the plasmodium parasite. the present study reports one of the first experimental infections of progeny from wild-caught an. funestus with the p. falciparum parasite providing a realistic avenue for the characterisation of immune responses as ...201627301693
antiplasmodial activity is an ancient and conserved feature of tick defensins.ancestral sequence reconstruction has been widely used to test evolution-based hypotheses. the genome of the european tick vector, ixodes ricinus, encodes for defensin peptides with diverse antimicrobial activities against distantly related pathogens. these pathogens include fungi, gram-negative, and gram-positive bacteria, i.e., a wide antimicrobial spectrum. ticks do not transmit these pathogens, suggesting that these defensins may act against a wide range of microbes encountered by ticks duri ...201627822206
malaria risk factor assessment using active and passive surveillance data from aceh besar, indonesia, a low endemic, malaria elimination setting with plasmodium knowlesi, plasmodium vivax, and plasmodium falciparum.as malaria transmission declines, it becomes more geographically focused and more likely due to asymptomatic and non-falciparum infections. to inform malaria elimination planning in the context of this changing epidemiology, local assessments on the risk factors for malaria infection are necessary, yet challenging due to the low number of malaria cases.201627619000
ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from alseodaphne corneri and dehaasia longipedicellata.the uv-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 m nacl, 35 degree celsius). the pk(a) values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. boldine 3 gave a pk(a) value of 9.16 and 10.44. all of the alkaloids 1-3 were stable at physiological ph; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of ...201626898753
epidemiology of plasmodium vivax malaria in peru.malaria in peru, dominated by plasmodium vivax, remains a public health problem. the 1990s saw newly epidemic malaria emerge, primarily in the loreto department in the amazon region, including areas near to iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal peru and the gold mining regions of southeastern peru. although a global fund-supported intervention (pamafro, 2005-2010) was temporally associated with a decrease of malaria tr ...201627799639
assessing parasite clearance during uncomplicated plasmodium falciparum infection treated with artesunate monotherapy in suriname.artemisinin resistance in plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. hence, a single-arm prospective efficacy trial was conducted in suriname for uncomplicated p. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatm ...201627920563
challenges for malaria elimination in brazil.brazil currently contributes 42 % of all malaria cases reported in the latin america and the caribbean, a region where major progress towards malaria elimination has been achieved in recent years. in 2014, malaria burden in brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. transmission in brazil remains entrenched in t ...201627206924
declining malaria transmission in rural amazon: changing epidemiology and challenges to achieve elimination.in recent years, considerable success in reducing its incidence has been achieved in brazil, leading to a relative increase in the proportion of cases caused by plasmodium vivax, considered a harder-to-eliminate parasite. this study aim is to describe the transmission dynamics and associated risk factors in a rural settlement area in the western brazilian amazon.201627165432
species-specific escape of plasmodium sporozoites from oocysts of avian, rodent, and human malarial parasites.malaria is transmitted when an infected mosquito delivers plasmodium sporozoites into a vertebrate host. there are many species of plasmodium and, in general, the infection is host-specific. for example, plasmodium gallinaceum is an avian parasite, while plasmodium berghei infects mice. these two parasites have been extensively used as experimental models of malaria transmission. plasmodium falciparum and plasmodium vivax are the most important agents of human malaria, a life-threatening disease ...201627480269
successful malaria elimination in the ecuador-peru border region: epidemiology and lessons learned.in recent years, malaria (plasmodium vivax and plasmodium falciparum) has been successfully controlled in the ecuador-peru coastal border region. the aim of this study was to document this control effort and to identify the best practices and lessons learned that are applicable to malaria control and to other vector-borne diseases. a proximal outcome evaluation was conducted of the robust elimination programme in el oro province, ecuador, and the tumbes region, peru. data collection efforts incl ...201627894320
epidemiology of plasmodium vivax in indonesia.endemic malaria occurs across much of the vast indonesian archipelago. all five species of plasmodium known to naturally infect humans occur here, along with 20 species of anopheles mosquitoes confirmed as carriers of malaria. two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in indonesia: plasmodium falciparum and plasmodium vivax the challenge posed by p. vivax is especially steep in indonesia because chloroquine-resistant strains predomi ...201627708185
global epidemiology of plasmodium vivax.plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against plasmodium falciparum unlike p. falciparum, p. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. these traits affect both its geographic distribution a ...201627402513
molecular analysis of pfs47-mediated plasmodium evasion of mosquito immunity.malaria is a life-threatening disease caused by plasmodium falciparum parasites that is transmitted through the bites of infected anopheline mosquitoes. p. falciparum dispersal from africa, as a result of human migration, required adaptation of the parasite to several different indigenous anopheline species. the mosquito immune system can greatly limit infection and p. falciparum evolved a strategy to evade these responses that is mediated by the pfs47 gene. pfs47 is a polymorphic gene with sign ...201627992481
plasmodium yoelii nigeriensis (n67) is a robust animal model to study malaria transmission by south american anopheline mosquitoes.malaria is endemic in the american continent and the amazonian rainforest is the region with the highest risk of transmission. however, the lack of suitable experimental models to infect malaria vectors from the americas has limited the progress to understand the biology of transmission in this region. anopheles aquasalis, a major vector in coastal areas of south america, was found to be highly refractory to infection with two strains of plasmodium falciparum (nf54 and 7g8) and with plasmodium b ...201627911924
population density, climate variables and poverty synergistically structure spatial risk in urban malaria in india.the world is rapidly becoming urban with the global population living in cities projected to double by 2050. this increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. in particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. interestingly india, as opposed to africa, har ...201627906962
demographic and clinical profiles of plasmodium falciparum and plasmodium vivax patients at a tertiary care centre in southwestern india.malaria remains an important cause of morbidity and mortality in india. though many comprehensive studies have been carried out in africa and southeast asia to characterize and examine determinants of plasmodium falciparum and plasmodium vivax malaria pathogenesis, fewer have been conducted in india.201627884146
a monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of plasmodium falciparum.the malaria vaccine candidate rts,s/as01 (gsk vaccines) induces high igg concentration against the circumsporozoite protein (csp) of plasmodium falciparum. in human vaccine recipients circulating anti-csp antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. however, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (mal1c), derived from a rts,s/as01-immunized volunteer, ...201627825382
safety and immunogenicity of pfs25-epa/alhydrogel®, a transmission blocking vaccine against plasmodium falciparum: an open label study in malaria naïve adults.transmission-blocking vaccines (tbvs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. pfs25 is a leading tbv candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to epa, a recombinant, detoxified exoprotein a from pseudomonas aeruginosa. in this report, we describe results of an open-label, dose-escalating phase 1 trial to assess the safety and immunogenicit ...201627749907
characterization of novel antimalarial compound act-451840: preclinical assessment of activity and dose-efficacy modeling.artemisinin resistance observed in southeast asia threatens the continued use of artemisinin-based combination therapy in endemic countries. additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. herein, the preclinical characterization of one of these com ...201627701420
genetic characterization of plasmodium putative pantothenate kinase genes reveals their essential role in malaria parasite transmission to the mosquito.the metabolic machinery for the biosynthesis of coenzyme a (coa) from exogenous pantothenic acid (vitamin b5) has long been considered as an excellent target for the development of selective antimicrobials. earlier studies in the human malaria parasite plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. although two eukaryotic-type putative pantothenate kinase genes (pank1 and pank2) have been identifie ...201627644319
an inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines.an effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. the standard membrane-feeding assay (smfa) for plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. while several studies have discussed the inherent variability ...201627612458
recent advances in malaria genomics and epigenomics.malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. however, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (plasmodium spp.) biology and its interactions with its host and vector. driven by the availability of vast amounts of genome sequence data from plasmodium species strains, relevant human population ...201627605022
human cd8+ t cells mediate protective immunity induced by a human malaria vaccine in human immune system mice.a number of studies have shown that cd8+ t cells mediate protective anti-malaria immunity in a mouse model. however, whether human cd8+ t cells play a role in protection against malaria remains unknown. we recently established human immune system (his) mice harboring functional human cd8+ t cells (his-cd8 mice) by transduction with hla-a∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. these his-cd8 mice mount a potent, antigen-specific ...201627502569
transcriptomic evidence for modulation of host inflammatory responses during febrile plasmodium falciparum malaria.identifying molecular predictors and mechanisms of malaria disease is important for understanding how plasmodium falciparum malaria is controlled. transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. in this prospective, proof-of-principle study, we compared whole-blood rna-seq profiles at pre-and post-infection time points from malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal pc ...201627506615
diagnosis and treatment based on quantitative pcr after controlled human malaria infection.controlled human malaria infection (chmi) has become well-established in the evaluation of drugs and vaccines. anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. this study explores the effects of using the more sensitive qpcr as the primary diagnostic test.201627495296
characterization of the plasmodium falciparum and p. berghei glycerol 3-phosphate acyltransferase involved in fasii fatty acid utilization in the malaria parasite apicoplast.malaria parasites can synthesize fatty acids via a type ii fatty acid synthesis (fasii) pathway located in their apicoplast. the fasii pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of fasii in human (plasmodium falciparum) and rodent (plasmodium berghei) malaria parasites and investigate how this enzyme contribu ...201627324409
phosphorylated and nonphosphorylated pfmap2 are localized in the nucleus, dependent on the stage of plasmodium falciparum asexual maturation.plasmodium falciparum mitogen-activated protein (map) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. our study shows for the first time that the p. falciparum specific map kinase 2 (pfmap2) is colocalized in the nucleus of all of the asexual erythrocytic stages of p. falciparum and is particularly elevated in its phosphorylated form. it was also discovered that pfmap2 is expressed i ...201627525262
mosquito bite immunization with radiation-attenuated plasmodium falciparum sporozoites: safety, tolerability, protective efficacy and humoral immunogenicity.in this phase 1 clinical trial, healthy adult, malaria-naïve subjects were immunized with radiation-attenuated plasmodium falciparum sporozoites (pfras) by mosquito bite and then underwent controlled human malaria infection (chmi). the pfras model for immunization against malaria had previously induced >90 % sterile protection against homologous chmi. this study was to further explore the safety, tolerability and protective efficacy of the pfras model and to provide biological specimens to chara ...201627448805
dynamics of gamete production and mating in the parasitic protist trypanosoma brucei.sexual reproduction in plasmodium falciparum and trypanosoma brucei occurs in the insect vector and is important in generating hybrid strains with different combinations of parental characteristics. production of hybrid parasite genotypes depends on the likelihood of co-infection of the vector with multiple strains. in mosquitoes, existing infection with plasmodium facilitates the establishment of a second infection, although the asynchronicity of gamete production subsequently prevents mating. ...201627439767
plasmodium adometdc/odc bifunctional enzyme is essential for male sexual stage development and mosquito transmission.polyamines are positively-charged organic molecules that are important for cellular growth and division. polyamines and their synthesizing enzymes are particularly abundant in rapidly proliferating eukaryotic cells such as parasitic protozoa and cancer cells. polyamine biosynthesis inhibitors, such as elfornithine, are now being considered for cancer prevention and have been used effectively against trypanosoma brucei inhibitors of polyamine biosynthesis have caused growth arrest of plasmodium f ...201627387533
malaria transmission potential could be reduced with current and future climate change.several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. however, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. we investigate how increases in temperature from optimal conditions (27 °c to 30 °c and 33 °c) interact with realistic diurnal temperature ranges (dtr: ± 0 °c, 3 °c, and 4.5 °c) to affect the ability of key vector spe ...201627324146
il-22 dampens the t cell response in experimental malaria.a tight regulation between the pro- and anti-inflammatory immune responses during plasmodial infection is of crucial importance, since a disruption leads to severe malaria pathology. il-22 is a member of the il-10 cytokine family, which is known to be highly important in immune regulation. we could detect high plasma levels of il-22 in plasmodium falciparum malaria as well as in plasmodium berghei anka (pba)-infected c57bl/6j mice. the deficiency of il-22 in mice during pba infection led to an e ...201627311945
safety and high level efficacy of the combination malaria vaccine regimen of rts,s/as01b with chimpanzee adenovirus 63 and modified vaccinia ankara vectored vaccines expressing me-trap.the need for a highly efficacious vaccine against plasmodium falciparum remains pressing. in this controlled human malaria infection (chmi) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (rts,s/as01b) and the other inducing potent t-cell responses to thrombospondin-related adhesion protein (trap) by using a viral vector.201627307573
the machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites.sequestration of red blood cells infected with the human malaria parasite plasmodium falciparum in organs such as the brain is considered important for pathogenicity. a similar phenomenon has been observed in mouse models of malaria, using the rodent parasite plasmodium berghei, but it is unclear whether the p. falciparum proteins known to be involved in this process are conserved in the rodent parasite. here we identify the p. berghei orthologues of two such key factors of p. falciparum, sbp1 a ...201627225796
analysis of the dose-dependent stage-specific in vitro efficacy of a multi-stage malaria vaccine candidate cocktail.the high incidence and mortality rate of malaria remains a serious burden for many developing countries, and a vaccine that induces durable and highly effective immune responses is, therefore, desirable. an earlier analysis of the stage-specific in vitro efficacy of a malaria vaccine candidate cocktail (vamax) considered the general properties of complex multi-component, multi-stage combination vaccines in rabbit immunization experiments using a hyper-immunization protocol featuring six consecut ...201627188716
a highly infectious plasmodium yoelii parasite, bearing plasmodium falciparum circumsporozoite protein.plasmodium circumsporozoite protein (csp) is a major surface antigen present in the sporozoite (spz) stage of a malaria parasite. rts, s vaccine, the most clinically advanced malaria vaccine, consists of a large portion of plasmodium falciparum csp (pfcsp). a highly infectious, recombinant rodent malaria, plasmodium yoelii parasite bearing a full-length pfcsp, pfcsp/py spz, was needed as a tool to evaluate the role of pfcsp in mediating, protective, anti-malaria immunity in a mouse model.201627068454
plasmodium falciparum cyclic amine resistance locus (pfcarl), a resistance mechanism for two distinct compound classes.mmv007564 is a novel antimalarial benzimidazolyl piperidine chemotype identified in cellular screens. to identify the genetic determinant of mmv007564 resistance, parasites were cultured in the presence of the compound to generate resistant lines. whole genome sequencing revealed distinct mutations in the gene named plasmodium falciparum cyclic amine resistance locus (pfcarl), encoding a conserved protein of unknown function. mutations in pfcarl are strongly associated with resistance to a struc ...201627933786
paratransgenesis to control malaria vectors: a semi-field pilot study.malaria still remains a serious health burden in developing countries, causing more than 1 million deaths annually. given the lack of an effective vaccine against its major etiological agent, plasmodium falciparum, and the growing resistance of this parasite to the currently available drugs repertoire and of anopheles mosquitoes to insecticides, the development of innovative control measures is an imperative to reduce malaria transmission. paratransgenesis, the modification of symbiotic organism ...201626965746
high heterogeneity of malaria transmission and a large sub-patent and diverse reservoir of infection in wusab as safil district, republic of yemen.yemen remains the country with the highest malaria transmission within the arabian peninsula and a source of imported cases to neighbouring countries.201627059182
low prevalence of plasmodium and absence of malaria transmission in conakry, guinea: prospects for elimination.over the past 15 years, mortality and morbidity due to malaria have been reduced substantially in sub-saharan africa and local elimination has been achieved in some settings. this study addresses the bio-ecology of larval and adult stages of malaria vectors, plasmodium infection in anopheles gambiae s.l. in the city of conakry, guinea, and discusses the prospect for malaria elimination.201626987480
treatment-seeking behaviour and associated costs for malaria in papua, indonesia.malaria remains a significant public health issue in eastern indonesia, where multidrug resistant plasmodium falciparum and plasmodium vivax are highly prevalent. the objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in mimika district, papua province in 2006.201627821127
plasmodium vivax infection: a major determinant of severe anaemia in infancy.most malarious countries outside of africa are co-endemic for plasmodium falciparum and plasmodium vivax. the comparative burden of anaemia in the community caused by these two species is incompletely characterized.201627306221
frequent blood feeding enables insecticide-treated nets to reduce transmission by mosquitoes that bite predominately outdoors.the effectiveness of vector control on malaria transmission by long-lasting insecticidal nets (llins) and indoor residual spraying (irs) depends on the vectors entering houses to blood feed and rest when people are inside houses. in the solomon islands, significant reductions in malaria have been achieved in the past 20 years with insecticide-treated bed nets, irs, improved diagnosis and treatment with artemisinin combination therapies; despite the preference of the primary vector, anopheles far ...201626969430
behaviour and molecular identification of anopheles malaria vectors in jayapura district, papua province, indonesia.members of the anopheles punctulatus group dominate papua, indonesia and papua new guinea (png), with a geographic range that extends south through vanuatu. an. farauti and an. punctulatus are the presumed major vectors in this region. although this group of species has been extensively studied in png and the southern archipelagoes within their range, their distribution, ecology and vector behaviours have not been well characterized in eastern indonesia.201627060058
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