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expression, characterization, and cellular localization of knowpains, papain-like cysteine proteases of the plasmodium knowlesi malaria parasite.papain-like cysteine proteases of malaria parasites degrade haemoglobin in an acidic food vacuole to provide amino acids for intraerythrocytic parasites. these proteases are potential drug targets because their inhibitors block parasite development, and efforts are underway to develop chemotherapeutic inhibitors of these proteases as the treatments for malaria. plasmodium knowlesi has recently been shown to be an important human pathogen in parts of asia. we report expression and characterizatio ...201223251596
[natural plasmodium knowlesi malaria infections in humans].the first reported case of natural transmission of plasmodium knowlesi to humans was published in 1965. in southeast asia, the atypical presentation of malaria cases, the changes in the distribution of the plasmodium species diagnosed and their atypical morphology prompted several studies that confirmed natural infections in humans by this protozoon which naturally infects different species of apes which are endemic in the forests of this region. recent studies suggest that p. knowlesi malaria i ...201223235820
laboratory markers of disease severity in plasmodium knowlesi infection: a case control study.plasmodium knowlesi malaria causes severe disease in up to 10% of cases in malaysian borneo and has a mortality rate of 1 - 2%. however, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of plasmodium.201223110615
deaths due to plasmodium knowlesi malaria in sabah, malaysia: association with reporting as plasmodium malariae and delayed parenteral artesunate.the simian parasite plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in sabah, malaysia, but is morphologically indistinguishable from and still commonly reported as plasmodium malariae, despite the paucity of this species in sabah. since december 2008 sabah department of health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. this paper reviews all malaria deaths in sabah subsequent to the ...201222905799
plasmodium knowlesi malaria: assessing the risk to the british armed forces.plasmodium knowlesi is a zoonosis and is now recognised as the fifth commonly occurring form of human malaria. it is endemic in south east asia, including some areas previously declared malaria free or at low risk for malaria. the epidemiology of the disease is very different to other forms of malaria which are determined by transmission by anthrophilic mosquitoes from human reservoirs. in contrast plasmodium knowlesi malaria has a monkey reservoir and disease is transmitted to humans by mosquit ...201223402069
[plasmodium knowlesi: an emerging species in humans?].plasmodium knowlesi is typically found in macaques and has recently been recognized as the fifth plasmodium species to cause malaria in humans. several cases of p. knowlesi malaria have been reported in people in southeast asia. most cases are simple but approximately one in 10 patients develops complications. the morphology of p. knowlesi parasites in human infections closely resembles that of plasmodium malariae or plasmodium falciparum, so a molecular method is the optimum diagnostic procedur ...201223353028
the n-terminal segment of plasmodium falciparum surfin4.1 is required for its trafficking to the red blood cell cytosol through the endoplasmic reticulum.plasmodium falciparum surfin is a type i transmembrane protein that shares domains with molecules expressed on the surface of the red blood cells (rbcs) infected with a variety of malaria parasite species, such as p. falciparum pfemp1, plasmodium vivax vir proteins, and plasmodium knowlesi sicavar. thus, understanding the export mechanism of surfin to the rbc may provide fundamental insights into how malaria parasites export their proteins to rbc cytosol in general. we re-evaluate surfin4.1 for ...201223287798
adaptation of the genetically tractable malaria pathogen plasmodium knowlesi to continuous culture in human erythrocytes.research into the aetiological agent of the most widespread form of severe malaria, plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. however, most malaria outside africa is caused by a distinct plasmodium species, plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite plasmodium knowlesi is a frequent cause of life-threatening malari ...201223267069
entomologic investigation of plasmodium knowlesi vectors in kuala lipis, pahang, malaysia.the first natural infection of plasmodium knowlesi in humans was recorded in 1965 in peninsular malaysia. extensive research was then conducted and it was postulated that it was a rare incident and that simian malaria will not be easily transmitted to humans. however, at the turn of the 21st century, knowlesi malaria was prevalent throughout southeast asia and is life threatening. thus, a longitudinal study was initiated to determine the vectors, their seasonal variation and preference to humans ...201222727041
Plasmodium knowlesi: A Malaria Parasite of Monkeys and Humans (*).Plasmodium knowlesi is a malaria parasite of monkeys of Southeast Asia that is transmitted by mosquitoes of the Anopheles leucosphyrus group. Humans are frequently infected with this parasite and misdiagnosed as being infected with Plasmodium malariae. The parasite was a major monkey animal model for developing antimalarial vaccines and investigations of the biology of parasite invasion. P. knowlesi is the first monkey malaria parasite genome to be sequenced and annotated.201222149265
Identification of Gene Encoding Plasmodium knowlesi Phosphatidylserine Decarboxylase by Genetic Complementation in Yeast and Characterization of in Vitro Maturation of Encoded Enzyme.The 23-megabase genome of Plasmodium falciparum, the causative agent of severe human malaria, contains ~5300 genes, most of unknown function or lacking homologs in other organisms. Identification of these gene functions will help in the discovery of novel targets for the development of antimalarial drugs and vaccines. The P. falciparum genome is unusually A + T-rich, which hampers cloning and expressing these genes in heterologous systems for functional analysis. The large repertoire of genetic ...201222057268
increased detection of plasmodium knowlesi in sandakan division, sabah as revealed by plasmonex™.plasmodium knowlesi is a simian malaria parasite that is widespread in humans in malaysian borneo. however, little is known about the incidence and distribution of this parasite in the sandakan division, malaysian borneo. therefore, the aim of the present epidemiological study was to investigate the incidence and distribution of p. knowlesi as well as other plasmodium species in this division based on a most recent developed hexaplex pcr system (plasmonex™).201323902626
colonization of anopheles cracens: a malaria vector of emerging importance.anopheles cracens has been incriminated as a vector for the simian malaria parasite, plasmodium knowlesi, that is the fifth plasmodium species infecting humans. little experimental data exists on this mosquito species due to the lack of its availability in laboratories.201323537404
immunogenicity of bacterial-expressed recombinant plasmodium knowlesi merozoite surface protein-142 (msp-142).plasmodium knowlesi is the fifth plasmodium species that can infect humans. the plasmodium merozoite surface protein-1(42) (msp-1(42)) is a potential candidate for malaria vaccine. however, limited studies have focused on p. knowlesi msp-1(42).201324354660
plasmodium knowlesi: the emerging zoonotic malaria parasite.plasmodium knowlesi was initially identified in the 30s as a natural plasmodium of macaca fascicularis monkey also capable of experimentally infecting humans. it gained a relative notoriety in the mid-30s as an alternative to plasmodium vivax in the treatment of the general paralysis of the insane (neurosyphilis). in 1965 the first natural human infection was described in a us military surveyor coming back from the pahang jungle of the malaysian peninsula. p. knowlesi was again brought to the at ...201323088834
kinetic modelling of phospholipid synthesis in plasmodium knowlesi unravels crucial steps and relative importance of multiple pathways.plasmodium is the causal parasite of malaria, infectious disease responsible for the death of up to one million people each year. glycerophospholipid and consequently membrane biosynthesis are essential for the survival of the parasite and are targeted by a new class of antimalarial drugs developed in our lab. in order to understand the highly redundant phospholipid synthethic pathways and eventual mechanism of resistance to various drugs, an organism specific kinetic model of these metabolic pa ...201324209716
spleen-dependent regulation of antigenic variation in malaria parasites: plasmodium knowlesi sicavar expression profiles in splenic and asplenic hosts.antigenic variation by malaria parasites was first described in plasmodium knowlesi, which infects humans and macaque monkeys, and subsequently in p. falciparum, the most virulent human parasite. the schizont-infected cell agglutination (sica) variant proteins encoded by the sicavar multigene family in p. knowlesi, and erythrocyte membrane protein-1 (emp-1) antigens encoded by the var multigene family in p. falciparum, are expressed at the surface of infected erythrocytes, are associated with vi ...201324205067
plasmodium knowlesi infection imported to germany, january 2013. 201324176659
malaria vectors in the greater mekong subregion: overview of malaria vectors and remaining challenges.malaria transmission in the greater mekong subregion depends on, among other factors, vector behavior and ecology, and the degree of contact between humans and the anopheles mosquitoes. this chapter will review and update knowledge presented in the 2003 mekong malaria monograph for planning and implementing evidence-based vector control programs. collation of 150 publications and reports showed that the highest number of vector species reported included an. minimus theobald complex (26.74%), an. ...201324159831
plasmodium knowlesi infection imported to germany, january 2013.plasmodium knowlesi was known as a plasmodium of macaques until p. knowlesi transmission to humans was recognised in borneo and later throughout south-east asia. we describe here a case of a p. knowlesi infection imported to germany from thailand. the patient had not taken antimalarial chemoprophylaxis and suffered from daily fever attacks. microscopy revealed trophozoites and gametocytes resembling p. malariae. p. knowlesi malaria was confirmed by pcr.201324128698
accurate identification of the six human plasmodium spp. causing imported malaria, including plasmodium ovale wallikeri and plasmodium knowlesi.accurate identification of plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. malaria is no longer endemic in italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among european non-endemic countries including france ...201324034175
a modified semi-nested multiplex malaria pcr (snm-pcr) for the identification of the five human plasmodium species occurring in southeast asia.we have modified an existing semi-nested multiplex polymerase chain reaction (pcr) by adding one plasmodium knowlesi-specific nested pcr, and validated the latter against laboratory and clinical samples. this new method has the advantage of being relatively affordable in low resource settings while identifying the five human plasmodium species with a three-step pcr.201323980132
cloning, expression, and immunocharacterization of surface protein containing an altered thrombospondin repeat domain (spatr) from plasmodium knowlesi.plasmodium knowlesi is the fifth species identified to cause malaria in humans and is often misdiagnosed as plasmodium malariae due to morphological similarities. the development of an inexpensive, serological detection method utilizing antibodies specific to p. knowlesi would be a valuable tool for diagnosis. however, the identification of specific antigens for these parasites remains a major challenge for generating such assays. in this study, surface protein containing an altered thrombospond ...201323734702
differential sequence diversity at merozoite surface protein-1 locus of plasmodium knowlesi from humans and macaques in thailand.to determine the genetic diversity and potential transmission routes of plasmodium knowlesi, we analyzed the complete nucleotide sequence of the gene encoding the merozoite surface protein-1 of this simian malaria (pkmsp-1), an asexual blood-stage vaccine candidate, from naturally infected humans and macaques in thailand. analysis of pkmsp-1 sequences from humans (n=12) and monkeys (n=12) reveals five conserved and four variable domains. most nucleotide substitutions in conserved domains were di ...201323727342
first case of plasmodium knowlesi infection in a japanese traveller returning from malaysia.this is the first case of plasmodium knowlesi infection in a japanese traveller returning from malaysia. in september 2012, a previously healthy 35-year-old japanese man presented to national center for global health and medicine in tokyo with a two-day history of daily fever, mild headaches and mild arthralgia. malaria parasites were found in the giemsa-stained thin blood smear, which showed band forms similar to plasmodium malariae. although a nested pcr showed the amplification of the primer ...201323587117
hyperparasitaemic human plasmodium knowlesi infection with atypical morphology in peninsular malaysia.plasmodium knowlesi is a potentially life-threatening zoonotic malaria parasite due to its relatively short erythrocytic cycle. microscopic identification of p. knowlesi is difficult, with "compacted parasite cytoplasm" being one of the important identifying keys. this report is about a case of hyperparasitaemic human p. knowlesi infection (27% parasitaemia) with atypical amoeboid morphology. a peninsular malaysian was admitted to the hospital with malaria. he suffered anaemia and acute kidney f ...201323496970
case report: fatal plasmodium knowlesi malaria following an atypical clinical presentation and delayed diagnosis. 201323466773
preclinical drug evaluation system in the plasmodium knowlesi baboon model of malaria: the methotrexate study.drug resistance against first-line antimalarials warrants search for new lead compounds and repurposing of drugs such as methotrexate. animal models are required for preclinical drug development before clinical testing. this study aimed to develop a preclinical drug development system in baboons infected with plasmodium knowlesi.201323294369
a prospective comparative study of knowlesi, falciparum, and vivax malaria in sabah, malaysia: high proportion with severe disease from plasmodium knowlesi and plasmodium vivax but no mortality with early referral and artesunate therapy.plasmodium knowlesi commonly causes severe malaria in malaysian borneo, with high case-fatality rates reported. we compared risk, spectrum, and outcome of severe disease from p. knowlesi, plasmodium falciparum, and plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.201323087389
is there a risk of suburban transmission of malaria in selangor, malaysia?the suburban transmission of malaria in selangor, malaysia's most developed and populous state still remains a concern for public health in this region. despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. in addition, cases of simian malaria caused by plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. the aim of this study was to investigate the possibility of local mala ...201324194901
increasing incidence of plasmodium knowlesi malaria following control of p. falciparum and p. vivax malaria in sabah, malaysia.the simian parasite plasmodium knowlesi is a common cause of human malaria in malaysian borneo and threatens the prospect of malaria elimination. however, little is known about the emergence of p. knowlesi, particularly in sabah. we reviewed sabah department of health records to investigate the trend of each malaria species over time.201323359830
plasmodium knowlesi infection: a diagnostic challenge.plasmodium knowlesi malaria is an uncommon, but highly prevalent parasitic infection in parts of malaysia. this is the case of a 14-year-old singaporean boy presenting to our emergency department with an 11-day history of fever following a school trip to malaysia. hepatosplenomegaly was the only clinical finding; laboratory tests showed thrombocytopaenia, lymphopaenia, mild anaemia and liver transaminitis. specific malaria antigen tests were negative, but the peripheral blood film showed plasmod ...201323608876
co-incidental plasmodium knowlesi and mucormycosis infections presenting with acute kidney injury and lower gastrointestinal bleeding.plasmodium knowlesi is frequently reported in southeast asian countries and is now widely regarded as the fifth malarial parasite. mucormycosis is a rare fungal infection that can occur in patients with a weakened immune system.201323826445
evaluation of the sensitivity of a pldh-based and an aldolase-based rapid diagnostic test for diagnosis of uncomplicated and severe malaria caused by pcr-confirmed plasmodium knowlesi, plasmodium falciparum, and plasmodium vivax.plasmodium knowlesi can cause severe and fatal human malaria in southeast asia. rapid diagnosis of all plasmodium species is essential for initiation of effective treatment. rapid diagnostic tests (rdts) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. at a tertiary referral hospital in sabah, malaysia, we prospectively evaluated the sensitivity of two combination rdts for the diagnosis of uncomplicated and ...201323345297
the evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (msp-9), in plasmodium vivax and closely related species.the merozoite surface protein-9 (msp-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. orthologs encoding this antigen have been found in all known species of plasmodium parasitic to primates. in order to characterize and investigate the extent and maintenance of msp-9 genetic diversity, we analyzed dna sequences of the following malaria parasite species: plasmodium falci ...201324044894
polymorphism of the parasite lactate dehydrogenase gene from plasmodium vivax korean isolates.assaying for the parasitic lactate dehydrogenase (pldh) is widely used as a rapid diagnostic test (rdt), but the efficacy of its serological effectiveness in diagnosis, that is antibody detection ability, is not known. the genetic variation of korean isolates was analysed, and recombinant protein pldh was evaluated as a serodiagnostic antigen for the detection of plasmodium vivax malaria.201323688062
evaluation of recombinant plasmodium knowlesi merozoite surface protein-1(33) for detection of human malaria.plasmodium knowlesi is now known as the fifth plasmodium species that can cause human malaria. the plasmodium merozoite surface protein (msp) has been reported to be potential target for vaccination and diagnosis of malaria. msp-1(33) has been shown to be immunogenic and its t cell epitopes could mediate cellular immune protection. however, limited studies have focused on p. knowlesi msp-133. in this study, an approximately 28-kda recombinant p. knowlesi msp-1(33) (pkmsp-1(33)) was expressed by ...201323509118
plasmodium vivax and plasmodium knowlesi: cloning, expression and functional analysis of 1-cys peroxiredoxin.malaria parasites like other aerobes need to detoxify the reactive oxygen species (ros) that are mainly produced from hemoglobin degradation in the food vacuole. since plasmodium lacks catalase and genuine glutathione peroxidase, they are highly dependent on peroxiredoxins (prxs) and superoxide dismutases for ros detoxification. prxs are protective antioxidant enzymes that act through reduction of hydrogen peroxides. in recent years, several studies have been done on prx family of human malaria ...201323178658
ex vivo culture of plasmodium vivax and plasmodium cynomolgi and in vitro culture of plasmodium knowlesi blood stages.long-term in vitro cultures of blood-stage parasites are so far feasible only for plasmodium falciparum and p. knowlesi. in this chapter, we describe short-term ex vivo culturing of p. cynomolgi and p. vivax. we also describe long-term in vitro culturing of p. knowlesi as well as some techniques for synchronizing parasites. cultured parasites can be used for a variety of purposes, e.g., for in vitro drug assays and antibody-mediated growth inhibition assays.201322990770
susceptibility of human plasmodium knowlesi infections to anti-malarials.evidence suggests that plasmodium knowlesi malaria in sarawak, malaysian borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. therefore, adequate response to available anti-malarial treatments is assumed.201324245918
plasmodium knowlesi and hiv co-infection in a german traveller to thailand.a case of plasmodium knowlesi and hiv co-infection is reported in a german traveller returning from thailand. the 54 year-old patient presented to the institute of tropical medicine in tübingen with a 11-day history of daily fever and chills. initial microscopic evaluation of giemsa-stained thin blood smears was suggestive of a mixed infection with plasmodium falciparum and plasmodium malariae. however, pcr amplification of small subunit ribosomal rna gene revealed a p. knowlesi infection. paras ...201323941258
development of monoclonal antibodies that target 1-cys peroxiredoxin and differentiate plasmodium falciparum from p. vivax and p. knowlesi.prompt and accurate diagnosis of malarial patients is a crucial factor in controlling the morbidity and mortality of the disease. effective treatment decisions require a correct diagnosis among mixed-species malarial patients. differential diagnosis is particularly important in cases of plasmodium vivax, a species that shares endemicity with p. falciparum in most endemic areas. moreover, it is difficult to identify p. knowlesi on the basis of morphology alone, and rapid diagnostic tests are stil ...201323874139
the structure of the d3 domain of plasmodium falciparum myosin tail interacting protein mtip in complex with a nanobody.apicomplexan parasites enter host cells by many sophisticated steps including use of an atp-powered invasion machinery. the machinery consists of multiple proteins, including a special myosin (myoa) which moves along an actin fiber and which is connected to the myosin tail interaction protein (mtip). here we report a crystal structure of the major myoa-binding domain (d3) of plasmodium falciparum mtip in complex with an anti-mtip nanobody. in this complex, the myoa-binding groove in mtip-d3 is c ...201323831371
the compact conformation of the plasmodium knowlesi myosin tail interacting protein mtip in complex with the c-terminal helix of myosin a.the myosin motor of the malaria parasite's invasion machinery moves over actin fibers while it is making critical contacts with the myosin-tail interacting protein (mtip). previously, in a "compact" plasmodium falciparum mtip•myoa complex, mtip domains 2 (d2) and 3 (d3) make contacts with the myoa helix, and the central helix is kinked, but in an "extended" plasmodium knowlesi mtip•myoa complex only d3 interacts with the myoa helix, and the central helix is fully extended. here we report the cry ...201323831369
multiplex 5' nuclease quantitative real-time pcr for clinical diagnosis of malaria and species-level identification and epidemiologic evaluation of malaria-causing parasites, including plasmodium knowlesi.molecular diagnosis of malaria offers many potential advantages over microscopy, including identification of malaria to the species level in an era with few experienced microscopists. we developed high-throughput multiplex 5' nuclease quantitative pcr (qpcr) assays, with the potential to support large studies, to specifically identify plasmodium falciparum, p. vivax, p. ovale, p. malariae, and p. knowlesi. we compared qpcr to microscopy and confirmed discordant results with an alternative target ...201323804387
plasmodium falciparum-like parasites infecting wild apes in southern cameroon do not represent a recurrent source of human malaria.wild-living chimpanzees and gorillas harbor a multitude of plasmodium species, including six of the subgenus laverania, one of which served as the progenitor of plasmodium falciparum. despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. here, we used plasmodium species-specific pcr, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern cameroon for ape laverania infections. among 1,402 blood samples, ...201323569255
expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans.the macaque malaria parasite plasmodium knowlesi has recently emerged as an important zoonosis in southeast asia. infections are typically mild but can cause severe disease, achieving parasite densities similar to fatal plasmodium falciparum infections. here we show that a primate-adapted p. knowlesi parasite proliferates poorly in human blood due to a strong preference for young red blood cells (rbcs). we establish a continuous in vitro culture system by using human blood enriched for young cel ...201323535659
an epidemiological overview of malaria in bangladesh.bangladesh is one of the four major malaria-endemic countries in south-east asia having approximately 34% of its population at risk of malaria. this paper aims at providing an overview of the malaria situation in this country. relevant information was retrieved from published articles and reports in pubmed and google scholar. malaria in bangladesh is concentrated in 13 districts with a prevalence ranging between 3.1% and 36%, and is mostly caused by plasmodium falciparum. geographical conditions ...201323434288
limitations of microscopy to differentiate plasmodium species in a region co-endemic for plasmodium falciparum, plasmodium vivax and plasmodium knowlesi.in areas co-endemic for multiple plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where plasmodium knowlesi also commonly occurs.201323294844
discordance in drug resistance-associated mutation patterns in marker genes of plasmodium falciparum and plasmodium knowlesi during coinfections.human plasmodium knowlesi infections have been reported from several south-east asian countries, excluding india, but its drug susceptibility profile in mixed-infection cases remains unknown.201323292346
in vivo imaging in nhp models of malaria: challenges, progress and outlooks.animal models of malaria, mainly mice, have made a large contribution to our knowledge of host-pathogen interactions and immune responses, and to drug and vaccine design. non-human primate (nhp) models for malaria are admittedly under-used, although they are probably closer models than mice for human malaria; in particular, nhp models allow the use of human pathogens (plasmodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium knowlesi). nhps, whether natural hosts or experimenta ...201424042056
disease progression in plasmodium knowlesi malaria is linked to variation in invasion gene family members.emerging pathogens undermine initiatives to control the global health impact of infectious diseases. zoonotic malaria is no exception. plasmodium knowlesi, a malaria parasite of southeast asian macaques, has entered the human population. p. knowlesi, like plasmodium falciparum, can reach high parasitaemia in human infections, and the world health organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. not all patients with p. kno ...201425121807
malaria: an update on current chemotherapy.chemotherapy of malaria has become a rapidly changing field. less than two decades ago, treatment regimens were increasingly bound to fail due to emerging drug resistance against 4-aminoquinolines and sulfa compounds. by now, artemisinin-based combination therapies (acts) constitute the standard of care for uncomplicated falciparum malaria and are increasingly also taken into consideration for the treatment of non-falciparum malaria.201425110058
a conserved domain targets exported phistb family proteins to the periphery of plasmodium infected erythrocytes.during blood-stage infection, malaria parasites export numerous proteins to the host erythrocyte. the poly-helical interspersed sub-telomeric (phist) proteins are an exported family that share a common 'presan' domain, and include numerous members in plasmodium falciparum, plasmodium vivax and plasmodium knowlesi. in p. falciparum, phist proteins have been implicated in protein trafficking and intercellular communication. a number of phist proteins are essential for parasite survival. here, we i ...201425106850
parasitic pneumonia and lung involvement.parasitic infestations demonstrated a decline in the past decade as a result of better hygiene practices and improved socioeconomic conditions. nevertheless, global immigration, increased numbers of the immunocompromised people, international traveling, global warming, and rapid urbanization of the cities have increased the susceptibility of the world population to parasitic diseases. a number of new human parasites, such as plasmodium knowlesi, in addition to many potential parasites, have urge ...201424995332
changing epidemiology of malaria in sabah, malaysia: increasing incidence of plasmodium knowlesi.while malaysia has had great success in controlling plasmodium falciparum and plasmodium vivax, notifications of plasmodium malariae and the microscopically near-identical plasmodium knowlesi increased substantially over the past decade. however, whether this represents microscopic misdiagnosis or increased recognition of p. knowlesi has remained uncertain.201425272973
immunochromatographic antigen testing alone is sufficient to identify asymptomatic refugees at risk of severe malaria presenting to a single health service in victoria.current screening guidelines for malaria in new refugees include a combination of thick and thin film examination and immunochromatographic antigen test (ict). however, as the prevalence of malaria in our population has decreased due to changing refugee demographics, we sought to determine if an ict alone can reliably exclude malaria in our asymptomatic refugee population.a retrospective analysis was conducted of all investigations for malaria performed from 1 august 2011 to 31 july 2013, includ ...201425158813
human red blood cell-adapted plasmodium knowlesi parasites: a new model system for malaria research.plasmodium knowlesi is a simian malaria parasite primarily infecting macaque species in southeast asia. although its capacity to infect humans has been recognized since the early part of the last century, it has recently become evident that human infections are widespread and potentially life threatening. historically, p.  knowlesi has proven to be a powerful tool in early studies of malaria parasites, providing key breakthroughs in understanding many aspects of plasmodium biology. however, the ...201424506567
first case of a naturally acquired human infection with plasmodium cynomolgi.since 1960, a total of seven species of monkey malaria have been reported as transmissible to man by mosquito bite: plasmodium cynomolgi, plasmodium brasilianum, plasmodium eylesi, plasmodium knowlesi, plasmodium inui, plasmodium schwetzi and plasmodium simium. with the exception of p. knowlesi, none of the other species has been found to infect humans in nature. in this report, it is described the first known case of a naturally acquired p. cynomolgi malaria in humans.the patient was a 39-year- ...201424564912
using infective mosquitoes to challenge monkeys with plasmodium knowlesi in malaria vaccine studies.when rhesus monkeys (macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. however, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. to better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was deve ...201424893777
plasmodium knowlesi thioredoxin peroxidase 1 binds to nucleic acids and has rna chaperone activity.malaria parasites are under oxidative attack throughout their life cycle in human body and mosquito vector. therefore, plasmodium antioxidant defenses are crucial for its survival and being considered as interesting target for antimalarial drug design. plasmodium knowlesi has emerged recently from its simian host to human in southeast asia and has been recognized as the fifth plasmodium species that can cause human malaria. in this study, we cloned and characterized thioredoxin peroxidase 1 from ...201425092384
genetic diversity, haplotypes and allele groups of duffy binding protein (pkdbpαii) of plasmodium knowlesi clinical isolates from peninsular malaysia.the monkey malaria parasite plasmodium knowlesi is now recognized as the fifth species of plasmodium that can cause human malaria. like the region ii of the duffy binding protein of p. vivax (pvdbpii), the region ii of the p. knowlesi duffy binding protein (pkdbpαii) plays an essential role in the parasite's invasion into the host's erythrocyte. numerous polymorphism studies have been carried out on pvdbpii, but none has been reported on pkdbpαii. in this study, the genetic diversity, haplotyes ...201424693997
factors that are associated with the risk of acquiring plasmodium knowlesi malaria in sabah, malaysia: a case-control study protocol.plasmodium knowlesi has long been present in malaysia, and is now an emerging cause of zoonotic human malaria. cases have been confirmed throughout south-east asia where the ranges of its natural macaque hosts and anopheles leucosphyrus group vectors overlap. the majority of cases are from eastern malaysia, with increasing total public health notifications despite a concurrent reduction in plasmodium falciparum and p. vivax malaria. the public health implications are concerning given p. knowlesi ...201425149186
a study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe plasmodium knowlesi malaria in sabah, malaysia (act know trial).malaria due to plasmodium knowlesi is reported throughout south-east asia, and is the commonest cause of it in malaysia. p. knowlesi replicates every 24 h and can cause severe disease and death. current 2010 who malaria treatment guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. artemisinin-combination therapies (act) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been pros ...201425138814
defining the geographical range of the plasmodium knowlesi reservoir.the simian malaria parasite, plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. because malaria caused by p. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. information is required on the occurrence of human cases in different locations, on which non-human primat ...201424676231
hiv treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo.we have previously shown that the hiv protease inhibitor lopinavir-ritonavir (lpv-rtv) and the antibiotic trimethoprim sulfamethoxazole (tmp-smx) inhibit plasmodium liver stages in rodent malarias and in vitro in p. falciparum. since clinically relevant levels are better achieved in the non-human-primate model, and since plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for p. falciparum infection, we investigated the antimalarial activity of ...201424988386
efficacy and safety of artemisinin combination therapy (act) for non-falciparum malaria: a systematic review.artemisinin combination therapy (act) is recommended as first-line treatment for uncomplicated plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (plasmodium vivax, plasmodium ovale and plasmodium malariae). a more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.201425428624
identification of protein markers in patients infected with plasmodium knowlesi, plasmodium falciparum and plasmodium vivax.malaria is caused by parasitic protozoans of the genus plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. for this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. the aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various plasmodium species, including p. knowlesi, p. vivax and p. falciparum. sera from malaria- ...201425372941
genome-wide patterns of genetic polymorphism and signatures of selection in plasmodium vivax.plasmodium vivax is the most prevalent human malaria parasite outside of africa. yet, studies aimed to identify genes with signatures consistent with natural selection are rare. here, we present a comparative analysis of the pattern of genetic variation of five sequenced isolates of p. vivax and its divergence with two closely related species, plasmodium cynomolgi and plasmodium knowlesi, using a set of orthologous genes. in contrast to plasmodium falciparum, the parasite that causes the most le ...201425523904
evaluation of codon optimized recombinant plasmodium knowlesi merozoite surface protein-119 (pkmsp-119) expressed in pichia pastoris.malaria causes high global mortality and morbidity annually. plasmodium knowlesi has been recognised as the fifth human plasmodium sp. and its infection is widely distributed in southeast asia. merozoite surface protein-119 (msp-119) appears as a potential candidate for malaria blood stage vaccine as it could induce protective immunity. in this study, codon optimized p. knowlesi msp-119 (pkmsp-119) was expressed and purified in yeast pichia pastoris expression system. the purified recombinant pr ...201425776601
mapping infectious disease landscapes: unmanned aerial vehicles and epidemiology.the potential applications of unmanned aerial vehicles (uavs), or drones, have generated intense interest across many fields. uavs offer the potential to collect detailed spatial information in real time at relatively low cost and are being used increasingly in conservation and ecological research. within infectious disease epidemiology and public health research, uavs can provide spatially and temporally accurate data critical to understanding the linkages between disease transmission and envir ...201425443854
genotyping of the duffy blood group among plasmodium knowlesi-infected patients in malaysia.the duffy blood group is of major interest in clinical medicine as it plays an important role in plasmodium knowlesi and plasmodium vivax infection. in the present study, the distribution of duffy blood group genotypes and allelic frequencies among p. knowlesi infected patients as well as healthy individuals in peninsular malaysia were determined. the blood group of 60 healthy blood donors and 51 p. knowlesi malaria patients were genotyped using allele specific polymerase chain reaction (asp-pcr ...201425268233
detection of plasmodium knowlesi dna in the urine and faeces of a japanese macaque (macaca fuscata) over the course of an experimentally induced infection.diagnostic techniques based on pcr for the detection of plasmodium dna can be highly sensitive and specific. the vast majority of these techniques rely, however, on the invasive sampling of blood from infected hosts. there is, currently, considerable interest in the possibility of using body fluids other than blood as sources of parasite dna for pcr diagnosis.201425239687
severe plasmodium knowlesi infection with multiorgan involvement in north east peninsular malaysia.plasmodium knowlesi has been recently identified as the "fifth human malaria species" following the discovery in malaysian borneo of a large focus of this simian malaria parasite in humans. even though it shares microscopic similarities with plasmodium malariae, it may cause severe illness with risk of fatality. we describe a case of p. knowlesi infection causing multi-organ failure in a patient who was successfully managed due to early recognition of the infection. clinicians in this region sho ...201424862042
plasmodium knowlesi: clinical presentation and laboratory diagnosis of the first human case in a scottish traveler.the first imported case of plasmodium knowlesi in scotland is described in a 33-year-old female with a travel history to borneo. the patient ceased to take antimalarial prophylaxis after 4 days of her 10-day visit and presented with a history of fever, rigor, vomiting, and diarrhea after 13 days on her return to the uk. malaria antigen detection using the optimal-it and binax-now kits was negative. unusual trophozoite-like structures were observed under microscopic examination and the identifica ...201424861374
challenges in diagnosis of plasmodium knowlesi infections.plasmodium knowlesi is the fifth species of plasmodium recently identified to cause human malaria. infections with p. knowlesi are currently being reported from south-east asian countries and the incidence is on the rise with a possibility of spread to the geographically contiguous countries. p. knowlesi infections can result in a high degree of parasitemia causing severe malaria in a larger proportion of infected individuals. if detected early and treated with appropriate antimicrobials, these ...201424754023
molecular epidemiology of the emerging human malaria parasite "plasmodium knowlesi".malaria is the most important parasitic disease with global concern. plasmodium knowlesi recently has emerged from its natural simian host as a significant cause of human malaria, particularly in malaysian borneo. therefore, it has been added as the fifth human plasmodium specie which is widely distributed in southeast asia. recent developments of new molecular tools enhanced our understanding about the key features of this malaria parasite. here, we review some of the ways in which molecular ap ...201424754022
plasmodium knowlesi and other blood parasites. 201424754018
combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria due to plasmodium knowlesi and other plasmodium species in sabah, malaysia.plasmodium knowlesi causes severe and fatal malaria in malaysia. microscopic misdiagnosis is common and may delay appropriate treatment. p. knowlesi can cross-react with "species-specific" parasite lactate dehydrogenase (pldh) monoclonal antibodies used in rapid diagnostic tests (rdts) to detect p. falciparum and p. vivax. at one tertiary-care hospital and two district hospitals in sabah, we prospectively evaluated two combination rdts for malaria diagnosis by using both a pan-plasmodium-pldh (p ...201424696029
plasmodium knowlesi in travellers, update 2014.since the initial discovery of plasmodium knowlesi in malaysia, cases have been reported from several neighbouring countries. tourism has also resulted in an increasing number of cases diagnosed in europe, america, and oceania. in this review we focus on the risk of the travel-associated acquisition of p. knowlesi malaria.201424631521
high prevalence and genetic diversity of plasmodium malariae and no evidence of plasmodium knowlesi in bangladesh.although the prevalence of malaria remains high in parts of bangladesh, there continues to be a substantial shortage of information regarding the less common malaria parasites such as plasmodium malariae or plasmodium knowlesi. recent studies indicate that p. malariae may be extremely rare, and so far, there are no data on the presence (or absence) of p. knowlesi in southeastern bangladesh. genus- and species-specific nested polymerase chain reaction (pcr) analysis of the small subunit ribosomal ...201424578257
evaluation of three rapid diagnostic tests for the detection of human infections with plasmodium knowlesi.plasmodium knowlesi, a malaria parasite of southeast asian macaques, infects humans and can cause fatal malaria. it is difficult to diagnose by microscopy because of morphological similarity to plasmodium malariae. nested pcr assay is the most accurate method to distinguish p. knowlesi from other plasmodium species but is not cost effective in resource-poor settings. rapid diagnostic tests (rdts) are recommended for settings where malaria is prevalent. in this study, the effectiveness of three r ...201424548805
transmission and control of plasmodium knowlesi: a mathematical modelling study.plasmodium knowlesi is now recognised as a leading cause of malaria in malaysia. as humans come into increasing contact with the reservoir host (long-tailed macaques) as a consequence of deforestation, assessing the potential for a shift from zoonotic to sustained p. knowlesi transmission between humans is critical.201425058400
plasmodium knowlesi malaria an emerging public health problem in hulu selangor, selangor, malaysia (2009-2013): epidemiologic and entomologic analysis.while transmission of the human plasmodium species has declined, a significant increase in plasmodium knowlesi/plasmodium malariae cases was reported in hulu selangor, selangor, malaysia. thus, a study was undertaken to determine the epidemiology and the vectors involved in the transmission of knowlesi malaria.201425223878
severe plasmodium knowlesi infection with multi-organ failure imported to germany from thailand/myanmar.during the last two decades human infections with plasmodium knowlesi are increasingly diagnosed in south east asia and have also been reported in travellers. a severe case of imported p. knowlesi infection in a 73-year old german is presented, who had been travelling through myanmar and thailand for three weeks. microscopy showed a parasitaemia of 3% and different parasite stages including band-forms resembling plasmodium malariae. due to the clinical picture of severe malaria and the microscop ...201425367021
zoonotic malaria - global overview and research and policy needs.the four main plasmodium species that cause human malaria, plasmodium falciparum, plasmodium vivax, plasmodium malariae, and plasmodium ovale, are transmitted between humans by mosquito vectors belonging to the genus anopheles. it has recently become evident that plasmodium knowlesi, a parasite that typically infects forest macaque monkeys, can be transmitted by anophelines to cause malaria in humans in southeast asia. plasmodium knowlesi infections are frequently misdiagnosed microscopically as ...201425184118
high proportion of knowlesi malaria in recent malaria cases in malaysia.plasmodium knowlesi is a simian parasite that has been recognized as the fifth species causing human malaria. naturally-acquired p. knowlesi infection is widespread among human populations in southeast asia. the aim of this epidemiological study was to determine the incidence and distribution of malaria parasites, with a particular focus on human p. knowlesi infection in malaysia.201424886266
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
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
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
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
enrichment of reticulocytes from whole blood using aqueous multiphase systems of polymers.this paper demonstrates the enrichment of reticulocytes by centrifuging whole blood through aqueous multiphase systems (ampss)-immiscible phases of solutions of polymers that form step-gradients in density. the interfaces of an amps concentrate cells; this concentration facilitates the extraction of blood enriched for reticulocytes. amps enrich reticulocytes from blood from both healthy and hemochromatosis donors. varying the osmolality and density of the phases of amps provides different levels ...201525263455
improved detection of malaria cases in island settings of vanuatu and kenya by pcr that targets the plasmodium mitochondrial cytochrome c oxidase iii (cox3) gene.detection of sub-microscopic parasitemia is crucial for all malaria elimination programs. pcr-based methods have proven to be sensitive, but two rounds of amplification (nested pcr) are often needed to detect the presence of plasmodium dna. to simplify the detection process, we designed a nested pcr method whereby only the primary pcr is required for the detection of the four major human plasmodium species. primers designed for the detection of the fifth species, plasmodium knowlesi, were not in ...201525256904
from protease to decarboxylase: the molecular metamorphosis of phosphatidylserine decarboxylase.phosphatidylserine decarboxylase (psds) play a central role in the synthesis of phosphatidylethanolamine in numerous species of prokaryotes and eukaryotes. psds are unusual decarboxylase containing a pyruvoyl prosthetic group within the active site. the covalently attached pyruvoyl moiety is formed in a concerted reaction when the psd proenzyme undergoes an endoproteolytic cleavage into a large β-subunit, and a smaller α-subunit, which harbors the prosthetic group at its n terminus. the mechanis ...201525724650
ritonavir-boosted indinavir but not lopinavir inhibits erythrocytic stage plasmodium knowlesi malaria in rhesus macaques.the inhibitive activities of the human immunodeficiency virus protease inhibitors ritonavir (rtv) boosted indinavir (idv) and rtv boosted lopinavir (lpv) for erythrocytic stage malaria were evaluated in rhesus macaques. the idv/rtv regimen effectively inhibits the replication of plasmodium knowlesi with clinically relevant doses, whereas the lpv/rtv regimen did not show activity against plasmodium infection.201525704890
apropos: plasmodium knowlesi malaria an emerging public health problem in hulu selangor, selangor, malaysia (2009-2013): epidemiologic and entomologic analysis.the use of detailed methodologies and legitimate settings justifications in spatial analysis is imperative to locating areas of significance. studies missing this action may enact interventions in improper areas.201525651916
an autochthonous case of severe plasmodium knowlesi malaria in thailand.a 58-year-old thai man was infected with plasmodium knowlesi in chantaburi province, eastern thailand. in addition to pyrexia, the patient developed hypotension, renal failure, jaundice, and severe thrombocytopenia. the parasitemia at the time of admission was 16.67% or ∼503,400 parasites/μl. with artesunate treatment and supportive care, the patient recovered uneventfully. the occurrence of complicated knowlesi malaria in a low-endemic area underscores the risk of high morbidity from this simia ...201525535314
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
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
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