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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
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
malaria by plasmodium knowlesi, a zoonosis transmitted by vectors. 201525851255
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
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
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
crystal structure of plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody.the malaria parasite plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in southeast asia. this species should therefore be targeted in vaccine and therapeutic strategies against human malaria. apical membrane antigen 1 (ama1), which plays a role in plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against p. falciparum. recent vacci ...201525886591
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
parasite accumulation in placenta of non-immune baboons during plasmodium knowlesi infection.placental malaria (pm) causes adverse pregnancy outcomes in the mother and her foetus. it is difficult to study pm directly in humans due to ethical challenges. this study set out to bridge this gap by determining the outcome of pm in non-immune baboons in order to develop a non-human primate model for the disease.201525889709
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
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
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
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
[monkey malaria (plasmodium knowlesi infection) after travelling to thailand].a case of malaria caused by plasmodium knowlesi is described in a 52-year-old female german traveler after returning from thailand. p. knowlesi is a parasite of macaques in southeast asia and has been recognized in recent years as an important and probably increasing cause of human malaria in some areas. at least 16 cases in international travelers have been published so far. this includes four cases imported to germany. all german patients visited forested areas in southern thailand inhabited b ...201526080720
autoantibody profile of patients infected with knowlesi malaria.autoantibodies or antibodies against self-antigens are produced either during physiological processes to maintain homeostasis or pathological process such as trauma and infection. infection with parasites including plasmodium has been shown to generally induce elevated self-antibody (autoantibody) levels. plasmodium knowlesi is increasingly recognized as one of the most important emerging human malaria in southeast asia that can cause severe infection leading to mortality. autoimmune-like phenom ...201526086445
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
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
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
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
investigations on the occurrence of plasmodium knowlesi in travellers returning from the endemic areas of simian malaria.malaria remains an important public health issue all over the world. among 5 plasmodium species invasive to humans, plasmodium knowlesi has been identified most recently. it is sometimes difficult to differentiate this species from p. malariae with the use of microscopic examination. however, p. knowlesi infection may be associated with rapidly increasing parasitaemia and severe clinical course with the risk of death. samples from polish travellers returning from areas where simian malaria is en ...201526394318
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
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
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
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
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
non-invasive surveillance for plasmodium in reservoir macaque species.primates are important reservoirs for human diseases, but their infection status and disease dynamics are difficult to track in the wild. within the last decade, a macaque malaria, plasmodium knowlesi, has caused disease in hundreds of humans in southeast asia. in order to track cases and understand zoonotic risk, it is imperative to be able to quantify infection status in reservoir macaque species. in this study, protocols for the collection of non-invasive samples and isolation of malaria para ...201526459307
plasmodium knowlesi as a threat to global public health.malaria is a tropical disease caused by protozoans of the plasmodium genus. delayed diagnosis and misdiagnosis are strongly associated with higher mortality. in recent years, a greater importance is attributed to plasmodium knowlesi, a species found mainly in southeast asia. routine parasitological diagnostics are associated with certain limitations and difficulties in unambiguous determination of the parasite species based only on microscopic image. recently, molecular techniques have been incr ...201526537037
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
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
cytokine expression in malaria-infected non-human primate placentas.malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (pm) leading to adverse consequences like pre-term deliveries and abortions. immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. the establishment of more animal models f ...201226623293
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
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
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
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
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
association between landscape factors and spatial patterns of plasmodium knowlesi infections in sabah, malaysia.the zoonotic malaria species plasmodium knowlesi has become the main cause of human malaria in malaysian borneo. deforestation and associated environmental and population changes have been hypothesized as main drivers of this apparent emergence. we gathered village-level data for p. knowlesi incidence for the districts of kudat and kota marudu in sabah state, malaysia, for 2008-2012. we adjusted malaria records from routine reporting systems to reflect the diagnostic uncertainty of microscopy fo ...026812373
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
plasmodium knowlesi and human malaria parasites in khan phu, vietnam: gametocyte production in humans and frequent co-infection of mosquitoes.four species of malaria parasite, plasmodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium knowlesi infect humans living in the khanh phu commune, khanh hoa province, vietnam. the latter species also infects wild macaque monkeys in this region. in order to understand the transmission dynamics of the three species, we attempted to detect gametocytes of the three species in the blood of infected individuals, and sporozoites in the salivary glands of mosquitoes from the same regi ...201727894375
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
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
genetic clustering and polymorphism of the merozoite surface protein-3 of plasmodium knowlesi clinical isolates from peninsular malaysia.the simian malaria parasite plasmodium knowlesi has been reported to cause significant numbers of human infection in south east asia. its merozoite surface protein-3 (msp3) is a protein that belongs to a multi-gene family of proteins first found in plasmodium falciparum. several studies have evaluated the potential of p. falciparum msp3 as a potential vaccine candidate. however, to date no detailed studies have been carried out on p. knowlesi msp3 gene (pkmsp3). the present study investigates th ...201728049516
malaria epidemiology in central myanmar: identification of a multi-species asymptomatic reservoir of infection.the spread of artemisinin-resistant plasmodium falciparum is a global health concern. myanmar stands at the frontier of artemisinin-resistant p. falciparum. myanmar also has the highest reported malaria burden in southeast asia; it is integral in the world health organization's plan to eliminate malaria in southeast asia, yet few epidemiological data exist for the general population in myanmar.201728056979
detection of plasmodium knowlesi, plasmodium falciparum and plasmodium vivax using loop-mediated isothermal amplification (lamp) in a co-endemic area in malaysia.plasmodium knowlesi is the most common cause of malaria in malaysia. however, microscopic diagnosis is inaccurate and rapid diagnostic tests (rdts) are insufficiently sensitive. pcr is sensitive and specific but not feasible at a district level. loop-mediated isothermal amplification (lamp) shows potential with only basic requirements. a commercially available lamp assay, the eiken loopamp™ malaria pan detection kit, is sensitive for plasmodium falciparum and plasmodium vivax, but has not previo ...201728086789
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
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
investigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data.in the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (acts). however the potential threat of act failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (nces) to target this disease. the primary sulfonamide (ps) moiety is a component of several clinical drugs, including those for treatment of kidney di ...201728129569
antibody-independent mechanisms regulate the establishment of chronic plasmodium infection.malaria is caused by parasites of the genus plasmodium. all human-infecting plasmodium species can establish long-lasting chronic infections(1-5), creating an infectious reservoir to sustain transmission(1,6). it is widely accepted that the maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation(7). however, genes involved in this process have been identified in only two of five human-infecting species: plasmodium falciparum and plasmodium knowlesi. furtherm ...201728165471
contribution of plasmodium knowlesi to multi-species human malaria infections in north sumatera, indonesia. 201728201638
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
plasmodium knowlesi. 201728230261
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
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
diagnostic challenges and case management of the first imported case of plasmodium knowlesi in sri lanka.sri lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. imported malaria remains a challenge to resurgence of the disease. the diagnostic challenges encountered and the rapid response initiated to manage a plasmodium infection, which was later confirmed as plasmodium knowlesi, the first reported case from sri lanka, is discussed.201728327145
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
world malaria report: time to acknowledge plasmodium knowlesi malaria.the 2016 world health organization (who) world malaria report documents substantial progress towards control and elimination of malaria. however, major challenges remain. in some regions of southeast asia, the simian parasite plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the world malaria report.201728359340
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
guest commentary: plasmodium knowlesi-need to diagnose in india. 201728459008
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
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
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
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
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
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
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