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plasmodium knowlesi gene expression differs in ex vivo compared to in vitro blood-stage cultures.plasmodium knowlesi is one of five plasmodium species known to cause malaria in humans and can result in severe illness and death. while a zoonosis in humans, this simian malaria parasite species infects macaque monkeys and serves as an experimental model for in vivo, ex vivo and in vitro studies. it has underpinned malaria discoveries relating to host-pathogen interactions, the immune response and immune evasion strategies. this study investigated differences in p. knowlesi gene expression in s ...201525880967
malaria by plasmodium knowlesi, a zoonosis transmitted by vectors. 201525851255
human infections with plasmodium knowlesi--zoonotic malaria.in 2004 a large focus of plasmodium knowlesi malaria was reported in the human population in sarawak, malaysian borneo. plasmodium knowlesi, a parasite of the south-east asian macaques (macaca fascicularis and macaca nemestrina), had entered the human population. plasmodium knowlesi is transmitted by the leucosphyrus group of anopheline mosquitoes and transmission is largely zoonotic and restricted to the jungle setting. humans entering jungle transmission sites are at risk. since 2004, human ca ...201525843504
plasmodium knowlesi genome sequences from clinical isolates reveal extensive genomic dimorphism.plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. the study of p. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating p. knowlesi genome sequences from archived clinical isolates. our patient sample collection consisted of frozen whole blood samples that contained excessive human dna contamin ...201525830531
plasmodium knowlesi malaria: overview focussing on travel-associated infections.in 2004, plasmodium knowlesi was first recognised as a relevant cause of human malaria in southeast asia. since then, p. knowlesi has been described from all southeast asian countries except laos and has become well-established as the fifth human malaria parasite and the first significant zoonotic plasmodium species. as countries endemic for p. knowlesi malaria are among the most popular and most highly visited international destinations, travel medicine experts should be aware about disease and ...201525821192
primate malarias: diversity, distribution and insights for zoonotic plasmodium.protozoans within the genus plasmodium are well-known as the causative agents of malaria in humans. numerous plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. current spillover of a monkey malaria, plasmodium knowlesi, in southeast asia h ...201528616467
isolation of invasive plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors.malaria symptoms and pathogenesis are caused by blood stage parasite burdens of plasmodium spp., for which invasion of red blood cells (rbcs) by merozoites is essential. successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding rbc invasion. to understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activ ...201526684675
plasmodium knowlesi: from severe zoonosis to animal model.plasmodium knowlesi malaria is a newly described zoonosis in southeast asia. similarly to plasmodium falciparum, p. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. interpretation of host-parasite interactions in studies of p. knowlesi malaria adds a counterpoint to studies on p. falciparum. however, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. plasmodium knowle ...201525837310
structure, function and inhibition of the phosphoethanolamine methyltransferases of the human malaria parasites plasmodium vivax and plasmodium knowlesi.phosphoethanolamine methyltransferases (pmts) catalyze the three-step methylation of phosphoethanolamine to form phosphocholine, a critical step in the synthesis of phosphatidylcholine in a select number of eukaryotes including human malaria parasites, nematodes and plants. genetic studies in the malaria parasite plasmodium falciparum have shown that the methyltransferase pfpmt plays a critical function in parasite development and differentiation. the presence of pmt orthologs in other malaria p ...201525761669
molecular investigation of mixed malaria infections in southwest saudi arabia.to investigate the incidence of mixed-species (ms) malaria infection, and compare the results with microscopically confirmed cases of malaria.201525719595
molecular detection of human plasmodium species in sabah using plasmonex™ multiplex pcr and hydrolysis probes real-time pcr.malaria is a vector borne-parasitic disease transmitted through the bite of the infective female anopheles mosquitoes. five plasmodium species have been recognized by world health organization (who) as the causative agents of human malaria. generally, microscopic examination is the gold standard for routine malaria diagnosis. however, molecular pcr assays in many cases have shown improvement on the sensitivity and specificity over microscopic or other immunochromatographic assays.201525651852
plasmodium knowlesi malaria during pregnancy.plasmodium knowlesi is the commonest cause of malaria in malaysia, but little is known regarding infection during pregnancy.201525301955
plasmodium knowlesi - an emerging pathogen.ten years have passed since the publication of a large focus of plasmodium knowlesi infections in the human population. the discovery was made during a molecular investigation of atypical p. malariae cases in the kapit health division, sarawak, malaysian borneo. patients were more symptomatic with higher parasite counts than expected in p. malariae infections. the investigation found only p. knowlesi dna present in patient blood samples. morphological similarity had allowed p. knowlesi to masque ...201526029250
recognition of human erythrocyte receptors by the tryptophan-rich antigens of monkey malaria parasite plasmodium knowlesi.the monkey malaria parasite plasmodium knowlesi also infect humans. there is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. therefore, we investigated here the binding ability of p. knowlesi tryptophan-rich antigens (pktrags) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites.201526393350
genetic polymorphism in domain i of the apical membrane antigen-1 among plasmodium knowlesi clinical isolates from peninsular malaysia.the simian malaria parasite plasmodium knowlesi is now recognized as a species that can cause human malaria. the first report of large scale human knowlesi malaria was in 2004 in malaysia borneo. since then, hundreds of human knowlesi malaria cases have been reported in southeast asia. the present study investigates the genetic polymorphism of p. knowlesi di domain of the apical membrane antigen-1 (ama-1), a protein considered as a promising vaccine candidate for malaria. the di domain of ama-1 ...201526384455
distinct genetic difference between the duffy binding protein (pkdbpαii) of plasmodium knowlesi clinical isolates from north borneo and peninsular malaysia.plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. the duffy binding protein of p. knowlesi (pkdbpαii) is essential for the parasite's invasion into human and monkey erythrocytes. a previous study on p. knowlesi clinical isolates from peninsular malaysia reported high level of genetic diversity in the pkdbpαii. furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group i and allele group ii. in the present ...201525890095
the plasmodium vivax rhoptry neck protein 5 is expressed in the apical pole of plasmodium vivax vcg-1 strain schizonts and binds to human reticulocytes.different proteins derived from the membrane or the apical organelles become involved in malarial parasite invasion of host cells. among these, the rhoptry neck proteins (rons) interact with a protein component of the micronemes to enable the formation of a strong bond which is crucial for the parasite's successful invasion. the present study was aimed at identifying and characterizing the ron5 protein in plasmodium vivax and evaluating its ability to bind to reticulocytes.201525888962
detection of human malaria using recombinant plasmodium knowlesi merozoire surface protein-1 (msp-1₁₉) expressed in escherichia coli.malaria remains one of the world's most important infectious diseases and is responsible for enormous mortality and morbidity. human infection with plasmodium knowlesi is widely distributed in southeast asia. merozoite surface protein-1₁₉ (msp-1₁₉), which plays an important role in protective immunity against asexual blood stage malaria parasites, appears as a leading immunogenic antigen of plasmodium sp. we evaluated the sensitivity and specificity of recombinant p. knowlesi msp-1₁₉ (rmsp-1₁₉) ...201525812552
cloning, expression and functional characterization of heme detoxification protein (hdp) from the rodent malaria parasite plasmodium vinckei.malaria parasite resides within the host red blood cells, where it degrades vast amount of haemoglobin. during haemoglobin degradation, toxic free heme is liberated which subsequently gets converted into hemozoin. this process is facilitated by action of various proteins viz. heme detoxification protein (hdp), and histidine rich proteins ii and iii (hrp ii & iii). out of these, hdp is the most potent in hemozoin formation and plays indispensible role for parasite survival. despite this, the deta ...201525891072
simian malaria in wild macaques: first report from hulu selangor district, selangor, malaysia.malaria is a vector-borne parasitic disease which is prevalent in many developing countries. recently, it has been found that plasmodium knowlesi, a simian malaria parasite can be life-threatening to humans. long-tailed macaques, which are widely distributed in malaysia, are the natural hosts for simian malaria, including p. knowlesi. the aim of the present study was to determine the prevalence of simian malaria parasites in long-tailed macaques in the district of hulu selangor, selangor, malays ...201526437652
the plasmodium class xiv myosin, myob, has a distinct subcellular location in invasive and motile stages of the malaria parasite and an unusual light chain.myosin b (myob) is one of the two short class xiv myosins encoded in the plasmodium genome. class xiv myosins are characterized by a catalytic "head," a modified "neck," and the absence of a "tail" region. myosin a (myoa), the other class xiv myosin in plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but myob is not well characterized. we analyzed the properties of myob using three parasite species as follows: plasmodium falciparu ...201525802338
genetic diversity and natural selection of the plasmodium knowlesi circumsporozoite protein nonrepeat regions.plasmodium knowlesi is a simian malaria parasite that has been identified to cause malaria in humans. to date, several thousand cases of human knowlesi malaria have been reported around southeast asia. thus far, there is no detailed study on genetic diversity and natural selection of p. knowlesi circumsporozoite protein (csp), a prominent surface antigen on the sporozoite of the parasite. in the present study, the genetic diversity and natural selection acting on the nonrepeat regions of the gen ...201526379157
neglected tropical diseases among the association of southeast asian nations (asean): overview and update.the ten member states of the association of southeast asian nations (asean) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (ntds). almost 200 million people live in extreme poverty in asean countries, mostly in the low or lower middle-income countries of indonesia, the philippines, myanmar, viet nam, and cambodia, and many of them are affected by at least one ntd. however, ntds are prevalent even among upper mi ...201525880767
seasonal and spatial dynamics of the primary vector of plasmodium knowlesi within a major transmission focus in sabah, malaysia.the simian malaria parasite plasmodium knowlesi is emerging as a public health problem in southeast asia, particularly in malaysian borneo where it now accounts for the greatest burden of malaria cases and deaths. control is hindered by limited understanding of the ecology of potential vector species.201526448052
population genomic structure and adaptation in the zoonotic malaria parasite plasmodium knowlesi.malaria cases caused by the zoonotic parasite plasmodium knowlesi are being increasingly reported throughout southeast asia and in travelers returning from the region. to test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from malaysian borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from peninsular malaysia and the philippines. ...201526438871
humans frequently exposed to a range of non-human primate malaria parasite species through the bites of anopheles dirus mosquitoes in south-central vietnam.recent studies have described natural human infections of the non-human primate parasites plasmodium knowlesi and plasmodium cynomolgi. in southeast asia, mosquitoes of the anopheles leucosphyrus group bite both humans and monkeys in the forest and thus offer a possible route for plasmodium species to bridge the species barrier. in this study we analysed the species composition of malarial sporozoites infecting the salivary glands of anopheles dirus in order to determine their potential role as ...201526178324
admixture in humans of two divergent plasmodium knowlesi populations associated with different macaque host species.human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. a major zoonosis is now occurring with plasmodium knowlesi from macaques in southeast asia, with a recent acceleration in numbers of reported cases particularly in malaysia. to investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of s ...201526020959
low levels of polymorphisms and no evidence for diversifying selection on the plasmodium knowlesi apical membrane antigen 1 gene.infection with plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in southeast asia. p. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the apical membrane antigen 1 (ama1). in order to determine genetic diversity of the ama1 gene and to identify epitopes of ama1 under strongest immune selection, the ama1 gene of 52 p. knowlesi isolates derived from human infections w ...201525881166
identification of circulating biomarkers in sera of plasmodium knowlesi-infected malaria patients--comparison against plasmodium vivax infection.plasmodium knowlesi was identified as the fifth major malaria parasite in humans. it presents severe clinical symptoms and leads to mortality as a result of hyperparasitemia in a short period of time. this study aimed to improve the current understanding of p. knowlesi and identify potential biomarkers for knowlesi malaria.201525656928
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
investigating the contribution of peri-domestic transmission to risk of zoonotic malaria infection in humans.in recent years, the primate malaria plasmodium knowlesi has emerged in human populations throughout south east asia, with the largest hotspot being in sabah, malaysian borneo. control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. it is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly invest ...201627741235
dihydrofolate-reductase mutations in plasmodium knowlesi appear unrelated to selective drug pressure from putative human-to-human transmission in sabah, malaysia.malaria caused by zoonotic plasmodium knowlesi is an emerging threat in eastern malaysia. despite demonstrated vector competency, it is unknown whether human-to-human (h-h) transmission is occurring naturally. we sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (sp) as a potential marker of h-h transmission.201626930493
predicting the geographical distributions of the macaque hosts and mosquito vectors of plasmodium knowlesi malaria in forested and non-forested areas.plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. information on p. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species.201627125995
estimating geographical variation in the risk of zoonotic plasmodium knowlesi infection in countries eliminating malaria.infection by the simian malaria parasite, plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of malaysia. despite being a serious public health concern, the geographical distribution of p. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. human cases have been confirmed in at least nine southeast asian countries, many of which are making progress towards eliminati ...201627494405
vertical stratification of adult mosquitoes (diptera: culicidae) within a tropical rainforest in sabah, malaysia.malaria cases caused by plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques, are increasing rapidly in sabah, malaysia. one hypothesis is that this increase is associated with changes in land use. a study was carried out to identify the anopheline vectors present in different forest types and to observe the human landing behaviour of mosquitoes.201627430261
non-human primate malaria parasites: out of the forest and into the laboratory.the study of malaria in the laboratory relies on either the in vitro culture of human parasites, or the use of non-human malaria parasites in laboratory animals. in this review, we address the use of non-human primate malaria parasite species (nhpmps) in laboratory research. we describe the features of the most commonly used nhpmps, review their contribution to our understanding of malaria to date, and discuss their potential contribution to future studies.201627748213
sequence diversity and positive selection at the duffy-binding protein genes of plasmodium knowlesi and p. cynomolgi: analysis of the complete coding sequences of thai isolates.plasmodium knowlesi and p. cynomolgi are simian malaria parasites capable of causing symptomatic human infections. the interaction between the duffy binding protein alpha on p. knowlesi merozoite and the duffy-antigen receptor for chemokine (darc) on human and macaque erythrocyte membrane is prerequisite for establishment of blood stage infection whereas darc is not required for erythrocyte invasion by p. cynomolgi. to gain insights into the evolution of the pkdbp gene family comprising pkdbpα, ...201627480919
distribution and prevalence of malaria parasites among long-tailed macaques (macaca fascicularis) in regional populations across southeast asia.plasmodium knowlesi and plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while plasmodium inui can be experimentally transmitted from macaques to humans. one of their major natural hosts, the long-tailed macaque (macaca fascicularis), is host to two other species of plasmodium (plasmodium fieldi and plasmodium coatneyi) and is widely distributed in southeast asia. this study aims to determine the distribution of wild ...201627590474
expression and evaluation of recombinant plasmodium knowlesi merozoite surface protein-3 (msp-3) for detection of human malaria.malaria remains a major health threat in many parts of the globe and causes high mortality and morbidity with 214 million cases of malaria occurring globally in 2015. recent studies have outlined potential diagnostic markers and vaccine candidates one of which is the merozoite surface protein (msp)-3. in this study, novel recombinant plasmodium knowlesi msp-3 was cloned, expressed and purified in an escherichia coli system. subsequently, the recombinant protein was evaluated for its sensitivity ...201627391270
genetic diversity and natural selection in the rhoptry-associated protein 1 (rap-1) of recent plasmodium knowlesi clinical isolates from malaysia.the plasmodium rhoptry-associated protein 1 (rap-1) plays a role in the formation of the parasitophorous vacuole following the parasite's invasion of red blood cells. although there is some evidence that the protein is recognized by the host's immune system, study of plasmodium falciparum rap-1 (pfrap-1) suggests that it is not under immune pressure. a previous study on five old (1953-1962) p. knowlesi strains suggested that rap-1 has limited genetic polymorphism and might be under negative sele ...201626847346
loop-mediated isothermal amplification assay for identification of five human plasmodium species in malaysia.the lack of rapid, affordable, and accurate diagnostic tests represents the primary hurdle affecting malaria surveillance in resource- and expertise-limited areas. loop-mediated isothermal amplification (lamp) is a sensitive, rapid, and cheap diagnostic method. five species-specific lamp assays were developed based on 18s rrna gene. sensitivity and specificity of lamp results were calculated as compared with microscopic examination and nested polymerase chain reaction. lamp reactions were highly ...201626598573
the role of plasmodium knowlesi in the history of malaria research.in recent years, a malaria infection of humans in south east asia, originally diagnosed as a known human-infecting species, plasmodium malariae, has been identified as a simian parasite, plasmodium knowlesi. this species had been subject to considerable investigation in monkeys since the 1930s. with the development of continuous culture of the erythrocytic stages of the human malarial parasite, plasmodium falciparum in 1976, the emphasis in research shifted away from knowlesi. however, its impor ...201627829470
expansion of lysine-rich repeats in plasmodium proteins generates novel localization sequences that target the periphery of the host erythrocyte.repetitive low complexity sequences, mostly assumed to have no function, are common in proteins that are exported by the malaria parasite into its host erythrocyte. we identify a group of exported proteins containing short lysine-rich tandemly repeated sequences that are sufficient to localize to the erythrocyte periphery, where key virulence-related modifications to the plasma membrane and the underlying cytoskeleton are known to occur. efficiency of targeting is dependent on repeat number, ind ...201627777305
plasmodium knowlesi skeleton-binding protein 1 localizes to the 'sinton and mulligan' stipplings in the cytoplasm of monkey and human erythrocytes.the malaria parasite, plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite plasmodium falciparum, but has been less described for other plasmodium species. for p. falciparum, the exported protein skeleton-binding protein 1 (pfsbp1 ...201627732628
regulation and essentiality of the star-related lipid transfer (start) domain-containing phospholipid transfer protein pfa0210c in malaria parasites.star-related lipid transfer (start) domains are phospholipid- or sterol-binding modules that are present in many proteins. start domain-containing proteins (start proteins) play important functions in eukaryotic cells, including the redistribution of phospholipids to subcellular compartments and delivering sterols to the mitochondrion for steroid synthesis. how the activity of the start domain is regulated remains unknown for most of these proteins. the plasmodium falciparum start protein pfa021 ...201627694132
transfusion-transmitted severe plasmodium knowlesi malaria in a splenectomized patient with beta-thalassaemia major in sabah, malaysia: a case report.transfusion-transmitted malaria (ttm) is a well-recognized risk of receiving blood transfusions, and has occurred with plasmodium falciparum, plasmodium vivax, plasmodium ovale, and plasmodium malariae. the simian parasite plasmodium knowlesi is also known to be transmissible through inoculation of infected blood, and this species is now the most common cause of malaria in malaysia with a high rate of severity and fatal cases reported. no confirmed case of accidental transfusion-transmitted p. k ...201627405869
climate, environment and transmission of malaria.malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus anopheles. the transmission of malaria requires the interaction between the host, the vector and the parasite.the four species of parasites responsible for human malaria are plasmodium falciparum, plasmodium ovale, plasmodium malariae and plasmodium vivax. occasionally humans can be infected by several simian species, like plasmodium knowlesi, recognised as a major cause of human ...201627367318
common asymptomatic and submicroscopic malaria infections in western thailand revealed in longitudinal molecular and serological studies: a challenge to malaria elimination.despite largely successful control efforts, malaria remains a significant public health problem in thailand. based on microscopy, the northwestern province of tak, once thailand's highest burden area, is now considered a low-transmission region. however, microscopy is insensitive to detect low-level parasitaemia, causing gross underestimation of parasite prevalence in areas where most infections are subpatent. the objective of this study was to assess the current epidemiology of malaria prevalen ...201627333893
investigation on possible transmission of monkeys' plasmodium to human in a populations living in the equatorial rainforest of the democratic republic of congo.plasmodiums are protozoa that may infect various hosts. only five species are now recognized as naturally parasitizing humans: plasmodium falciparum, plasmodium vivax, plasmodium malariae, plasmodium ovale and plasmodium knowlesi. this fifth species, p. knowlesi, previously identified as naturally parasitizing the monkey macaca fascicularis, has been microscopically confused for a long time with p. malariae or p. falciparum and it was not possible to correctly differentiate them until the advent ...201627141437
adaptation of the [3h]hypoxanthine uptake assay for in vitro-cultured plasmodium knowlesi malaria parasites.the zoonotic malaria parasite plasmodium knowlesi has recently been established in continuous in vitro culture. here, the plasmodium falciparum [(3)h]hypoxanthine uptake assay was adapted for p. knowlesi and used to determine the sensitivity of this parasite to chloroquine, cycloguanil, and clindamycin. the data demonstrate that p. knowlesi is sensitive to all drugs, with 50% inhibitory concentrations (ic50s) consistent with those obtained with p. falciparum this assay provides a platform to use ...201627114276
a zoonotic human infection with simian malaria, plasmodium knowlesi, in central kalimantan, indonesia.the indonesian archipelago is endemic for malaria. although plasmodium falciparum and p. vivax are the most common causes for malaria cases, p. malariae and p. ovale are also present in certain regions. zoonotic case of malaria had just became the attention of public health communities after the serawak study in 2004. however, zoonotic case in indonesia is still under reported; only one published report of knowlesi malaria in south kalimantan in 2010.201627083152
clinical implications of a gradual dormancy concept in malaria.malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. currently, two distinct types of malaria recurrences are defined: recrudescence and relapse. a recrudescence is thought to originate from circulating plasmodium blood stages which do not cause fever before a certain level of a microscopically detectable parasitemia is reached. contrary, a relapse is thought to originate from quiescent intracel ...201627079460
uk malaria treatment guidelines 2016.1.malaria is the tropical disease most commonly imported into the uk, with 1300-1800 cases reported each year, and 2-11 deaths. 2. approximately three quarters of reported malaria cases in the uk are caused by plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. most non-falciparum malaria cases are caused by plasmodium vivax; a few cases are caused by the other species of plasmodium: pl ...201626880088
falling plasmodium knowlesi malaria death rate among adults despite rising incidence, sabah, malaysia, 2010-2014.deaths from plasmodium knowlesi malaria have been linked to delayed parenteral treatment. in malaysia, early intravenous artesunate is now recommended for all severe malaria cases. we describe p. knowlesi fatalities in sabah, malaysia, during 2012-2014 and report species-specific fatality rates based on 2010-2014 case notifications. sixteen malaria-associated deaths (caused by pcr-confirmed p. knowlesi [7], p. falciparum [7], and p. vivax [1] and microscopy-diagnosed "p. malariae" [1]) were repo ...201626690736
intravascular haemolysis with haemoglobinuria in a splenectomized patient with severe plasmodium knowlesi malaria.haemoglobinuria is an uncommon complication of severe malaria, reflecting acute intravascular haemolysis and potentially leading to acute kidney injury. it can occur early in the course of infection as a consequence of a high parasite burden, or may occur following commencement of anti-malarial treatment. treatment with quinine has been described as a risk factor; however the syndrome may also occur following treatment with intravenous artesunate. in malaysia, plasmodium knowlesi is the most com ...201627613607
[the first monkey malaria in turkey: a case of plasmodium knowlesi].plasmodium knowlesi is now added to the known four plasmodium species (p.vivax, p.falciparum, p.malariae, p.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern asia. p.knowlesi which infects macaque monkeys (macaca fascicularis and m.nemestrina) is transmitted to humans especially by anopheles leucosphyrus and an.hackeri mosquitos. first human cases of p.knowlesi malaria have been detected in malaysia which have reached hi ...201627525405
phylogeographic evidence for 2 genetically distinct zoonotic plasmodium knowlesi parasites, malaysia.infections of humans with the zoonotic simian malaria parasite plasmodium knowlesi occur throughout southeast asia, although most cases have occurred in malaysia, where p. knowlesi is now the dominant malaria species. this apparently skewed distribution prompted an investigation of the phylogeography of this parasite in 2 geographically separated regions of malaysia, peninsular malaysia and malaysian borneo. we investigated samples collected from humans and macaques in these regions. haplotype n ...201627433965
normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite plasmodium knowlesi.the dominant cause of malaria in malaysia is now plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout south east asia. comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human rbcs identified a genomic deletion that includes the gene encoding normocyte-binding protein xa (nbpxa) in parasites growing in cynomolgus rbcs but not in human rbcs. experimental deletion of the nbpxa gene in parasites adapted to growth in human ...201627303038
current status of plasmodium knowlesi vectors: a public health concern?plasmodium knowlesi a simian malaria parasite is currently affecting humans in southeast asia. malaysia has reported the most number of cases and p. knowlesi is the predominant species occurring in humans. the vectors of p. knowlesi belong to the leucosphyrus group of anopheles mosquitoes. these are generally described as forest-dwelling mosquitoes. with deforestation and changes in land-use, some species have become predominant in farms and villages. however, knowledge on the distribution of th ...201627222102
genetic diversity, natural selection and haplotype grouping of plasmodium knowlesi gamma protein region ii (pkγrii): comparison with the duffy binding protein (pkdbpαrii).plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in southeast asia. this parasite invades the erythrocytes of humans and of its natural host, the macaque macaca fascicularis, via interaction between the duffy binding protein region ii (pkdbpαrii) and the duffy antigen receptor on the host erythrocytes. in contrast, the p. knowlesi gamma protein region ii (pkγrii) is not involved in the invasion of p. knowlesi into humans. pkγrii, however, mediate ...201627195821
a sensitive, colorimetric, high-throughput loop-mediated isothermal amplification assay for the detection of plasmodium knowlesi.the simian parasite plasmodium knowlesi is now the commonest cause of malaria in malaysia and can rapidly cause severe and fatal malaria. however, microscopic misdiagnosis of plasmodium species is common, rapid antigen detection tests remain insufficiently sensitive and confirmation of p. knowlesi requires polymerase chain reaction (pcr). thus available point-of-care diagnostic tests are inadequate. this study reports the development of a simple, sensitive, colorimetric, high-throughput loop-med ...201627162264
clustering and genetic differentiation of the normocyte binding protein (nbpxa) of plasmodium knowlesi clinical isolates from peninsular malaysia and malaysia borneo.the zoonotic malaria parasite plasmodium knowlesi has become an emerging threat to south east asian countries particular in malaysia. a recent study from sarawak (malaysian borneo) discovered two distinct normocyte binding protein xa (pknbpxa) types of p. knowlesi. in the present study, the pknbpxa of clinical isolates from peninsular malaysia and sabah (malaysian borneo) were investigated for the presence of pknbpxa types and natural selection force acting on the gene.201627118390
invasion characteristics of a plasmodium knowlesi line newly isolated from a human.plasmodium knowlesi is extensively used as an important malaria model and is now recognized as an important cause of human malaria in malaysia. the strains of p. knowlesi currently used for research were isolated many decades ago, raising concerns that they might no longer be representative of contemporary parasite populations. we derived a new p. knowlesi line (university malaya line, um01), from a patient admitted in kuala lumpur, malaysia, and compared it with a human-adapted laboratory line ...201627097521
ancient human sialic acid variant restricts an emerging zoonotic malaria parasite.plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in southeast asia. plasmodium parasites bind to red blood cell (rbc) surface receptors, many of which are sialylated. while macaques synthesize the sialic acid variant n-glycolylneuraminic acid (neu5gc), humans cannot because of a mutation in the enzyme cmah that converts n-acetylneuraminic acid (neu5ac) to neu5gc. here we reconstitute cmah in human rbcs for the reintroduction of neu5gc, which results ...201627041489
rapid-antigen test negative malaria in a traveler returning from thailand, molecularly diagnosed as plasmodium knowlesi.plasmodium knowlesi has been identified in the last decade as a fifth species causing malaria in areas of south east asia. due to its short erythrocytic cycle, rapid development of high parasitemia and severe manifestations are frequently observed. therefore, prompt diagnosis of infection is essential to prevent complications, but the low sensitivity of rapid diagnostic tests for p knowlesi pose a diagnostic challenge in acute settings. in this study, we report the case of a german traveler to t ...201627006963
protective effect of chronic schistosomiasis in baboons coinfected with schistosoma mansoni and plasmodium knowlesi.malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. however, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. to examine this interaction, we conducted a randomized controlled study using the baboon (papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. two groups of baboons (n = ...201626883586
plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis.the public health threat posed by zoonotic plasmodium knowlesi appears to be growing: it is increasingly reported across south east asia, and is the leading cause of malaria in malaysian borneo. plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. the development of new quantitative approaches that ...201626817785
utility of cox1 phylogenetics to differentiate between locally acquired and imported plasmodium knowlesi infections in singapore.although there have been several phylogenetic studies on plasmodium knowlesi (p. knowlesi), only cytochrome c oxidase subunit 1 (cox1) gene analysis has shown some geographical differentiation between the isolates of different countries.201626805667
retinal changes in uncomplicated and severe plasmodium knowlesi malaria.plasmodium knowlesi causes severe malaria, but its pathogenesis is poorly understood. retinal changes provide insights into falciparum malaria pathogenesis but have not been studied in knowlesi malaria.201626671886
identification and characterization of epitopes on plasmodium knowlesi merozoite surface protein-142 (msp-142) using synthetic peptide library and phage display library.plasmodium knowlesi can cause potentially life threatening human malaria. the plasmodium merozoite surface protein-142 (msp-142) is a potential target for malaria blood stage vaccine, and for diagnosis of malaria. two epitope mapping techniques were used to identify the potential epitopes within p. knowlesi msp-142. nine and 14 potential epitopes were identified using overlapping synthetic peptide library and phage display library, respectively. two regions on p. knowlesi msp-142 (amino acid res ...201626624919
artesunate-mefloquine versus chloroquine for treatment of uncomplicated plasmodium knowlesi malaria in malaysia (act know): an open-label, randomised controlled trial.the zoonotic parasite plasmodium knowlesi has become the most common cause of human malaria in malaysia and is present throughout much of southeast asia. no randomised controlled trials have been done to identify the optimum treatment for this emerging infection. we aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated p knowlesi malaria in adults and children.201626603174
a case of severe plasmodium knowlesi in a splenectomized patient.plasmodium knowlesi, a zoonotic malaria, is now considered the fifth species of plasmodium causing malaria in humans. with its 24-hour erythrocytic stage of development, it has raised concern regarding its high potential in replicating and leading to severe illness. spleen is an important site for removal of parasitized red blood cells and generating immunity. we reported a case of knowlesi malaria in a non-immune, splenectomized patient. we observed the delay in parasite clearance, high parasit ...201626454133
asymptomatic and submicroscopic carriage of plasmodium knowlesi malaria in household and community members of clinical cases in sabah, malaysia.although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic plasmodium knowlesi parasitemia is unknown. in this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic p. knowlesi in this population. four published molecular assays were used to confirm the presence of p. knowlesi. latent class analysis revealed that the estimated proporti ...201626433222
plasmodium knowlesi: a relevant, versatile experimental malaria model.the primate malaria plasmodium knowlesi has a long-standing history as an experimental malaria model. studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite-host interactions. the adaptation to long-term in vitro continuous blood stage culture in rhesus monkey, macaca fascicularis and human red blood cells, as well ...201627938428
the treatment of plasmodium knowlesi malaria.plasmodium knowlesi occurs across southeast asia and is the most common cause of malaria in malaysia. high parasitaemias can develop rapidly, and the risk of severe disease in adults is at least as high as in falciparum malaria. prompt initiation of effective treatment is therefore essential. intravenous artesunate is highly effective in severe knowlesi malaria and in those with moderately high parasitaemia but otherwise uncomplicated disease. both chloroquine and artemisinin-combination therapy ...201727707609
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
fast and robust single pcr for plasmodium sporozoite detection in mosquitoes using the cytochrome oxidase i gene.molecular tools for detecting malaria-infected mosquitoes with improved practicality, sensitivity and specificity, and high-throughput are required. a common pcr technique used to detect mosquitoes infected with plasmodium spp. is a nested pcr assay based on the 18s-rrna gene. however, this technique has several technical limitations, is laborious and time consuming.201728569159
malaria pathogenesis.in the mosquito-human life cycle, the six species of malaria parasites infecting humans (plasmodium falciparum, plasmodium vivax, plasmodium ovale wallickeri, plasmodium ovale curtisi, plasmodium malariae, and plasmodium knowlesi) undergo 10 or more morphological states, replicate from single to 10,000+ cells, and vary in total population from one to many more than 10(6) organisms. in the human host, only a small number of these morphological stages lead to clinical disease and the vast majority ...201728533315
nested multiplex pcr for identification and detection of human plasmodium species including plasmodium knowlesi.to develop a new technique for diagnosis of plasmodium knowlesi and at the same time to be able to discriminate among the diverse species of plasmodium causing human malaria.201728442114
rapid detection of plasmodium knowlesi by isothermal recombinase polymerase amplification assay.in this study, we developed a recombinase polymerase amplification (rpa) assay for specific diagnosis of plasmodium knowlesi. genomic dna was extracted from whole blood samples using a commercial kit. with incubation at 37°c, the samples were successfully amplified within 20 minutes. the end product of rpa was further examined by loading onto agarose gel and a specific band was observed with a size of 128 bp. the rpa assay exhibited high sensitivity with limits of detection down to one copy of t ...201728820700
over two decades of plasmodium knowlesi infections in sarawak: trend and forecast.malaria is still of great public health concern, especially in malaysian borneo. the aim of this study was to determine the trends of p. knowlesi infection in sarawak, malaysia and to forecast the incidence of p. knowlesi until the year 2040. data on p. knowlesi malaria cases from 1992 to the year 2014 were obtained from the sarawak health department, malaysia. arima model was applied to forecast the future incidence of p. knowlesi infection. the data for the whole of sarawak and subsequently th ...201728768148
individual-level factors associated with the risk of acquiring human plasmodium knowlesi malaria in malaysia: a case-control study.the emergence of human malaria due to the monkey parasite plasmodium knowlesi threatens elimination efforts in southeast asia. changes in land use are thought to be driving the rise in reported p knowlesi cases, but the role of individual-level factors is unclear. to address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk.201728758162
pacbio assembly of a plasmodium knowlesi genome sequence with hi-c correction and manual annotation of the sicavar gene family.plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout south east asia. the p. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in plasmodium species, including a global view of several multigene families, such as the large sicavar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. however, repetitive dna sequences ...201728720171
evaluation of electric nets as means to sample mosquito vectors host-seeking on humans and primates.plasmodium knowlesi is found in macaques and is the only major zoonotic malaria to affect humans. transmission of p. knowlesi between people and macaques depends on the host species preferences and feeding behavior of mosquito vectors. however, these behaviours are difficult to measure due to the lack of standardized methods for sampling potential vectors attracted to different host species. this study evaluated electrocuting net traps as a safe, standardised method for sampling p. knowlesi vect ...201728720113
strict tropism for cd71+/ cd234+ human reticulocytes limits plasmodium cynomolgi's zoonotic potential.two malaria parasites of southeast asian macaques, plasmodium knowlesi and p. cynomolgi, can infect humans experimentally. in malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. by contrast, to date only a single case of naturally acquired p. cynomolgi has been found in humans. in this study we show that whereas p. cynomolgi merozoites invade monkey red blood cells (rbcs) indiscriminately in vitro, for hum ...201728698207
plasmodium knowlesi malaria in a traveller returning from the philippines to italy, 2016.plasmodium knowlesi is a simian parasite responsible for most human cases of malaria in malaysian borneo. a timely recognition of infection is crucial because of the risk of severe disease due to the rapid increase in parasitemia. we report a case of p. knowlesi infection in a traveller who developed fever and thrombocytopenia after returning from the philippines in 2016. rapid antigen test was negative, microscopy examination showed parasites similar to plasmodium malariae, with a parasite coun ...201728675245
genetic diversity in the c-terminus of merozoite surface protein 1 among plasmodium knowlesi isolates from selangor and sabah borneo, malaysia.plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. despite the significance of p. knowlesi malaria in parts of southeast asia, very little is known about the genetic variation in this parasite. our aim here was to explore sequence variation in a molecule called the 42kda merozoite surface protein-1 (msp-1), which is found on the surface of blood stages of plasmodium spp. and plays a key role in erythrocyte invasion. several studies of p. falcipar ...201728634105
guest commentary: plasmodium knowlesi-need to diagnose in india. 201728459008
the duffy binding protein (pkdbpαii) of plasmodium knowlesi from peninsular malaysia and malaysian borneo show different binding activity level to human erythrocytes.the zoonotic plasmodium knowlesi is a major cause of human malaria in malaysia. this parasite uses the duffy binding protein (pkdbpαii) to interact with the duffy antigen receptor for chemokines (darc) receptor on human and macaque erythrocytes to initiate invasion. previous studies on p. knowlesi have reported distinct peninsular malaysia and malaysian borneo pkdbpαii haplotypes. in the present study, the differential binding activity of these haplotypes with human and macaque (macaca fascicula ...201728800732
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
plasmodium knowlesi invasion following spread by infected mosquitoes, macaques and humans.plasmodium knowlesi is increasingly recognized as a major cause of malaria in southeast asia. anopheles leucosphyrous group mosquitoes transmit the parasite and natural hosts include long-tailed and pig-tailed macaques. despite early laboratory experiments demonstrating successful passage of infection between humans, the true role that humans play in p. knowlesi epidemiology remains unclear. the threat posed by its introduction into immunologically naïve populations is unknown despite being a pu ...201728345507
three divergent subpopulations of the malaria parasite plasmodium knowlesi.multilocus microsatellite genotyping of plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of borneo, each associated with a different macaque reservoir host species. geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland southeast asia and borneo. to resolve the overall population structure, multilocus microsatellite genotyping was conducted on a ...201728322705
targeting pyrimidine pathway of plasmodium knowlesi: new strategies towards identification of novel antimalarial chemotherapeutic agents.plasmodium knowlesi has been recently recognized as a human malarial parasite, particularly in the region of south-east asia. the effective prevention and treatment of this disease is increasingly bound to fail due to the emergence of drug resistance. hence, design of new drugs against known targets is gaining importance. pyrimidine pathway is a crucial metabolic pathway in p. knowlesi, and the enzymes involved are also unique in terms of their structure and function as compared to its human cou ...201728302017
plasmodium knowlesi. 201728230261
severe plasmodium knowlesi with dengue coinfection.we report a case of severe plasmodium knowlesi and dengue coinfection in a previously healthy 59-year-old malay man who presented with worsening shortness of breath, high-grade fever with chills and rigors, dry cough, myalgia, arthralgia, chest discomfort and poor appetite of 1 week duration. there was a history mosquito fogging around his neighbourhood in his hometown. further history revealed that he went to a forest in jeli (northern part of kelantan) 3 weeks prior to the event. initially he ...201728219910
contribution of plasmodium knowlesi to multi-species human malaria infections in north sumatera, indonesia. 201728201638
clinical features and management of plasmodium knowlesi infections in humans.plasmodium knowlesi is a simian malaria of primarily the macaque species of south east asia. while it was known that human infections could be induced during the years of malariotherapy, naturally occurring p. knowlesi human infections were thought to be rare. however, in 2004, knowlesi infections became recognized as an important infection amongst human populations in sarawak, malaysian borneo. since then, it has become recognized as a disease affecting people living and visiting endemic areas ...201728122651
avian and simian malaria: do they have a cancer connection?it has been claimed that infectious agents transmitted by mosquitoes (diptera: culicidae) may have a greater connection to cancer then hitherto supposed and that the immune system struggles to recognize and fight some of these infectious agents. one of the claims made is that there is a connection between human malaria and brain cancers in the usa. however, the usa declared itself free of human malaria in the last century, yet cancer incidences remain high, suggesting any overall cancer connecti ...201728019000
the dangers of accepting a single diagnosis: case report of concurrent plasmodium knowlesi malaria and dengue infection.dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. the first case reported was in 2005. since then, several concurrent infections have been reported between the dengue virus (denv) and the malaria protozoans, plasmodium falciparum and plasmodium vivax. symptoms of each infection may be mas ...201728049485
effect of clinically approved hdac inhibitors on plasmodium, leishmania and schistosoma parasite growth.malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. in this study, four clinically approved anti-cancer drugs (vorinostat, belinostat, panobinostat and romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity ...201728107750
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