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laser capture microdissection enables transcriptomic analysis of dividing and quiescent liver stages of plasmodium relapsing species.dormant liver stage forms (hypnozoites) of the malaria parasite plasmodium vivax present major hurdles to control and eradicate infection. despite major research efforts, the molecular composition of hypnozoites remains ill defined. here, we applied a combination of state-of-the-art technologies to generate the first transcriptome of hypnozoites. we developed a robust laser dissection microscopy protocol to isolate individual plasmodium cynomolgi hypnozoites and schizonts from infected monkey he ...201728256794
malaria eradication and the hidden parasite reservoir.accumulation of erythrocytic parasites in bone marrow and the spleen has been reported in cases of plasmodium vivax malaria. if this occurs commonly, these stages represent a possible source of early, relapse-like homologous recurrences. moreover, they might hinder the elimination of malaria from human populations. pertinent research suggestions have been made.201728366603
molecular characterization and phylogenetic analysis of plasmodium vivax, plasmodium falciparum, plasmodium ovale, plasmodium malariae and plasmodium cynomolgi.18s ribosomal rna gene sequences of different species of plasmodium were aligned and analyzed to determine the molecular diversity among different species of plasmodium. at content of p. cynomolgi, p. ovale, p. falciparum, p. vivax and p. malariae ranged from 62.30 to 63.15, 63.90 to 65.29, 66.67 to 68.40, 61.66 to 63.25 and 64.09 to 76.36 in case respectively. gc content of p. cynomolgi, p. ovale, p. falciparum, p. vivaxand p. malariae ranged from 36.85 to 37.70, 34.71 to 36.43, 31.60 to 33.27, ...201728316417
ancestry, plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (macaca fascicularis) bred for export in chinese breeding farms.most cynomolgus macaques (macaca fascicularis) used in the united states as animal models are imported from chinese breeding farms without documented ancestry. cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model.201728266719
case report: severe and complicated cynomolgi malaria in a rhesus macaque resulted in similar histopathological changes as those seen in human malaria.histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. animal models of malaria are critical to complement such studies. here, the histopathological changes observed in a rhesus macaque with severe and complicated plasmodium cynomolgi malaria are reported. the animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. the macaque was given subcurative antimalarial treatment, fluid s ...201728829738
an improved plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion.plasmodium cynomolgi, a non-human primate malaria parasite species, has been an important model parasite since its discovery in 1907. similarities in the biology of p. cynomolgi to the closely related, but less tractable, human malaria parasite p. vivax make it the model parasite of choice for liver biology and vaccine studies pertinent to p. vivax malaria. molecular and genome-scale studies of p. cynomolgi have relied on the current reference genome sequence, which remains highly fragmented wit ...201728748222
antimalarial efficacy of mmv390048, an inhibitor of plasmodium phosphatidylinositol 4-kinase.as part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. stemming from this series, we found that the derivative, mmv390048, lacked cross-resistance with current drugs used to treat malaria. this compound was efficacious against all plasmodium life cycle stages, apart from late hypnozoites in the liver. efficacy was shown in the humanized plasmodium fa ...201728446690
pi4 kinase is a prophylactic but not radical curative target in plasmodium vivax-type malaria parasites.two plasmodium pi4 kinase (pi4k) inhibitors, kdu691 and lmv599, were selected for in vivo testing as causal prophylactic and radical-cure agents for plasmodium cynomolgi sporozoite-infected rhesus macaques, based on their in vitro activity against liver stages. animals were infected with p. cynomolgi sporozoites, and compounds were dosed orally. both the kdu691 and lmv599 compounds were fully protective when administered prophylactically, and the more potent compound lmv599 achieved protection a ...201626926645
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
characterizing the genetic diversity of the monkey malaria parasite plasmodium cynomolgi.plasmodium cynomolgi is a malaria parasite that typically infects asian macaque monkeys, and humans on rare occasions. p. cynomolgi serves as a model system for the human malaria parasite plasmodium vivax, with which it shares such important biological characteristics as formation of a dormant liver stage and a preference to invade reticulocytes. while genomes of three p. cynomolgi strains have been sequenced, genetic diversity of p. cynomolgi has not been widely investigated. to address this we ...201626980604
characterization of caveola-vesicle complexes (cvcs) protein, phist/cvc-8195 in plasmodium vivax.plasmodium vivax produces numerous caveola-vesicle complex (cvc) structures beneath the membrane of infected erythrocytes. recently, a member helical interspersed subtelomeric (phist) superfamily protein, pcyphist/cvc-8195, was identified as cvcs-associated protein in plasmodium cynomolgi and essential for survival of this parasite. very little information has been documented to date about phist/cvc-8195 protein in p. vivax. in this study, the recombinant pvphist/cvc-8195 n and c termini were ex ...201628095657
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
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
plasmodium cynomolgi infections in rhesus macaques display clinical and parasitological features pertinent to modelling vivax malaria pathology and relapse infections.plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with p. vivax, including relapses. here, the haematological dynamics and clinical presentation of sporozoite-initiated p. cynomolgi infections in macaca mulatta (rhesus macaques) are evaluated over a 100-day period.201627590312
evolution of the transmission-blocking vaccine candidates pvs28 and pvs25 in plasmodium vivax: geographic differentiation and evidence of positive selection.transmission-blocking (tb) vaccines are considered an important tool for malaria control and elimination. among all the antigens characterized as tb vaccines against plasmodium vivax, the ookinete surface proteins pvs28 and pvs25 are leading candidates. these proteins likely originated by a gene duplication event that took place before the radiation of the known plasmodium species to primates. we report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. our result ...201627347876
contrasting infection susceptibility of the japanese macaques and cynomolgus macaques to closely related malaria parasites, plasmodium vivax and plasmodium cynomolgi.although the human malaria parasite plasmodium vivax is closely related to asian old world monkey malaria parasites, there are no reports of p. vivax infections in macaques. in this study, we compared the infectivity of p. vivax and plasmodium cynomolgi in japanese macaques (macaca fuscata) and in cynomolgus macaques (macaca fascicularis). the japanese macaques were highly susceptible to p. cynomolgi but not to p. vivax, whereas cynomolgus macaques showed mild/limited p. cynomolgi infection and ...201525316604
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
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
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
the biology of plasmodium vivax explored through genomics.malaria is a mosquito-borne disease caused by the plasmodium parasite. of the four plasmodium species that routinely cause human malaria, plasmodium vivax is the most widespread species outside africa, causing ∼18.9 million cases in 2012. p. vivax cannot be cultured continuously in vitro, which severely hampers research in nonendemic and endemic countries alike. consequently, whole-genome sequencing has become an effective means to interrogate the biology of the p. vivax parasite. our comparativ ...201525693446
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
heterogeneous genetic diversity pattern in plasmodium vivax genes encoding merozoite surface proteins (msp) -7e, -7f and -7l.the msp-7 gene has become differentially expanded in the plasmodium genus; plasmodium vivax has the highest copy number of this gene, several of which encode antigenic proteins in merozoites.201425496322
genetic diversity and natural selection of three blood-stage 6-cys proteins in plasmodium vivax populations from the china-myanmar endemic border.pv12, pv38 and pv41, the three 6-cys family proteins which are expressed in the blood-stage of vivax malaria, might be involved in merozoite invasion activity and thus be potential vaccine candidate antigens of plasmodium vivax. however, little information is available concerning the genetic diversity and natural selection of these three proteins. in the present study, we analyzed the amino acid sequences of p. vivax blood-stage 6-cys family proteins in comparison with the homologue proteins of ...201425266249
causal prophylactic efficacy of primaquine, tafenoquine, and atovaquone-proguanil against plasmodium cynomolgi in a rhesus monkey model.since the 1940s, the large animal model to assess novel causal prophylactic antimalarial agents has been the plasmodium cynomolgi sporozoite-infected indian-origin rhesus monkey. in 2009 the model was reassessed with 3 clinical standards: primaquine (pq), tafenoquine (tq), and atovaquone-proguanil. both control monkeys were parasitemic on day 8 post-sporozoite inoculation on day 0. primaquine at 1.78 mg base/kg/day on days (-1) to 8 protected 1 monkey and delayed parasitemia patency of the other ...201424780070
persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures.malaria relapses, resulting from the activation of quiescent hepatic hypnozoites of plasmodium vivax and plasmodium ovale, hinder global efforts to control and eliminate malaria. as primaquine, the only drug capable of eliminating hypnozoites, is unsuitable for mass administration, an alternative drug is needed urgently. currently, analyses of hypnozoites, including screening of compounds that would eliminate them, can only be made using common macaque models, principally macaca rhesus and macac ...201424509527
identification of a vir-orthologous immune evasion gene family from primate malaria parasites.the immune evasion gene family of malaria parasites encodes variant surface proteins that are expressed at the surface of infected erythrocytes and help the parasite in evading the host immune response by means of antigenic variation. the identification of plasmodium vivax vir orthologous immune evasion gene family from primate malaria parasites would provide new insight into the evolution of virulence and pathogenesis. three vir subfamilies viz. vir-b, vir-d and vir-g were successfully pcr ampl ...201424477117
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
neither the hiv protease inhibitor lopinavir-ritonavir nor the antimicrobial trimethoprim-sulfamethoxazole prevent malaria relapse in plasmodium cynomolgi-infected non-human primates.plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause p. vivax relapses. hiv and p. vivax malaria geographically overlap in many areas of the world, including south america and asia. despite the increasing body of knowledge regarding hiv protease inhibitors (hiv pis) on p. falciparum malaria, there are no data regarding the effects of these treatments on p. vivax's hypnozoite form and clinical ...201425541998
anti-relapse activity of mirincamycin in the plasmodium cynomolgi sporozoite-infected rhesus monkey model.mirincamycin is a close analog of the drug clindamycin used to treat plasmodium falciparum blood stages. the clinical need to treat plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.201425326032
pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (macaca mulatta).primaquine (pq) remains the sole available drug to prevent relapse of plasmodium vivax malaria more than 60 years after licensure. while this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the ...201425267666
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
efficacy of intravenous methylene blue, intravenous artesunate, and their combination in preclinical models of malaria.intravenous artesunate (iv as) is the present treatment of choice for severe malaria, but development of artemisinin resistance indicates that a further agent will be needed. methylene blue (mb) is an approved human agent for iv and oral use, and is already being investigated for oral treatment of uncomplicated malaria. to initiate investigation of iv mb for severe malaria, the efficacy of iv mb was compared to iv as and to their combination in rat and non-human primate malaria models.201425336091
kai407, a potent non-8-aminoquinoline compound that kills plasmodium cynomolgi early dormant liver stage parasites in vitro.preventing relapses of plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. for future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. a new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of plasmodium cynomolgi (an exce ...201324366744
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
triangular test design to evaluate tinidazole in the prevention of plasmodium vivax relapse.there are very few drugs that prevent the relapse of plasmodium vivax malaria in man. tinidazole is a 5-nitroimidazole approved in the usa for the treatment of indications including amoebiasis and giardiasis. in the non-human primate relapsing plasmodium cynomolgi/macaque malaria model, tinidazole cured one of six macaques studied with an apparent mild delay to relapse in the other five of 14-28 days compared to 11-12 days in controls. one study has demonstrated activity against p. vivax in man. ...201323718705
transgenic fluorescent plasmodium cynomolgi liver stages enable live imaging and purification of malaria hypnozoite-forms.a major challenge for strategies to combat the human malaria parasite plasmodium vivax is the presence of hypnozoites in the liver. these dormant forms can cause renewed clinical disease after reactivation through unknown mechanisms. the closely related non-human primate malaria p. cynomolgi is a frequently used model for studying hypnozoite-induced relapses. here we report the generation of the first transgenic p. cynomolgi parasites that stably express fluorescent markers in liver stages by tr ...201323359816
plasmodium vivax: modern strategies to study a persistent parasite's life cycle.plasmodium vivax has unique attributes to support its survival in varying ecologies and climates. these include hypnozoite forms in the liver, an invasion preference for reticulocytes, caveola-vesicle complex structures in the infected erythrocyte membrane and rapidly forming and circulating gametocytes. these characteristics make this species very different from p. falciparum. plasmodium cynomolgi and other related simian species have identical biology and can serve as informative models of p. ...201323384620
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
genomic insights into the other malaria.plasmodium vivax has received less attention and study than plasmodium falciparum, due in part to difficulties in culturing this pathogen. whole-genome sequencing of both p. vivax and plasmodium cynomolgi and characterization of genetic variation in these species provide a genetic toolbox for tertian malaria and new insights into the monkey malaria clade.201222932497
strain-specific protective effect of the immunity induced by live malarial sporozoites under chloroquine cover.the efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. in the present work, we have studied the strain-specificity of live sporozoite-induced ...201223029282
[stabilities of two kinds of plasmodium antigen substrate slides under different storage temperatures and time].to observe and compare the inspection effects of antigen substrate slides of plasmodium cynomolgi (p. c) and plasmodium falciparum (p. f) on the malaria antibody titer under different storage temperatures and time.201223012960
generation of quinolone antimalarials targeting the plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria.there is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. a failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. here we prese ...201222566611
plasmodium cynomolgi genome sequences provide insight into plasmodium vivax and the monkey malaria clade.p. cynomolgi, a malaria-causing parasite of asian old world monkeys, is the sister taxon of p. vivax, the most prevalent malaria-causing species in humans outside of africa. because p. cynomolgi shares many phenotypic, biological and genetic characteristics with p. vivax, we generated draft genome sequences for three p. cynomolgi strains and performed genomic analysis comparing them with the p. vivax genome, as well as with the genome of a third previously sequenced simian parasite, plasmodium k ...201222863735
a class of tricyclic compounds blocking malaria parasite oocyst development and transmission.malaria is a deadly infectious disease in many tropical and subtropical countries. previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. atp-binding cassette (abc) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. to investigate whether a plasmodiu ...201223129054
characterization of peripheral blood t lymphocyte subsets in chinese rhesus macaques with repeated or long-term infection with plasmodium cynomolgi.t lymphocytes play a vital role in antimalaria immunity, but there is little information about the role of t cells in malaria infection. in order to explore the profile of t cells in malaria immunity, we infected chinese rhesus macaques with the malaria parasite (plasmodium cynomolgi) and examined the dynamics of t cell subsets. both repeated and long-term infections were involved. our results showed that the monkeys in the repeated infection group acquired protective immunity through primary in ...201121842385
antimalarial effects of human immunodeficiency virus protease inhibitors in rhesus macaques.the antimalarial activity of the human immunodeficiency virus protease inhibitors indinavir and saquinavir was evaluated in rhesus macaques for the first time. indinavir effectively suppressed the growth of plasmodium cynomolgi and plasmodium knowlesi in vivo after a 7- or 3-day treatment, respectively, with clinically relevant doses, whereas saquinavir showed only weak activity against p. cynomolgi.201121486958
synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives.a series of 2-guanidino-4-oxoimidazoline (deoxo-iz) derivatives was prepared and showed potent antimalarial activities in rodent and rhesus models. compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in rhesus monkeys infected with sporozoites of plasmodium cynomolgi. the meta ...201121627120
radical curative efficacy of tafenoquine combination regimens in plasmodium cynomolgi-infected rhesus monkeys (macaca mulatta).abstract: background: tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of plasmodium vivax. during monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (g6pd) deficiency is a concern. combination with other antimalarials may mitigate these concerns. methods: in 2005, the radical curative efficacy of tafenoquine combinations was investigated in plasmodium cynom ...201121801400
evolutionary analysis of circumsporozoite surface protein and merozoite surface protein-1 (csp and msp-1) sequences of malaria parasites.malaria, one of the world's most common diseases, is caused by the intracellular protozoan parasite known as plasmodium. in this study, we have determined the evolutionary relationship of two single-copy proteins, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1), among plasmodium species using various bioinformatics tools and softwares. these two proteins are major blood stage antigens of plasmodium species. this study demonstrates that the circumsporozoite protein of plasm ...201121769195
Dormancy in mammalian malaria.This analysis principally concerns biological aspects of dormancy in mammalian malaria, with particular reference to the hypnozoite. Research is needed to reveal what happens to sporozoites of Plasmodium cynomolgi between the time of inoculation and when hypnozoites are first seen in the liver 36-40h later. It is likely that hypnozoites of relapsing malarial parasites will prove to be directly sporozoite-derived rather than merozoite-derived. There is indirect evidence that, contrary to what is ...201122118814
suppression of plasmodium cynomolgi in rhesus macaques by coinfection with babesia microti.both plasmodium and babesia species are intraerythrocytic protozoans that infect a wide range of hosts, including humans, and they elicit similar inflammatory responses and clinical manifestations that differ markedly in severity. we recently reported that a rhesus macaque that was chronically infected with babesia microti was able to control infection with plasmodium cynomolgi (a parasite of macaques with characteristics very similar to those of plasmodium vivax) better than naïve monkeys. to c ...201020048045
evidence for negative selection on the gene encoding rhoptry-associated protein 1 (rap-1) in plasmodium spp.assessing how natural selection, negative or positive, operates on genes with low polymorphism is challenging. we investigated the genetic diversity of orthologous genes encoding the rhoptry-associated protein 1 (rap-1), a low polymorphic protein of malarial parasites that is involved in erythrocyte invasion. we applied evolutionary genetic methods to study the polymorphism in rap-1 from plasmodium falciparum (n=32) and plasmodium vivax (n=6), the two parasites responsible for most human malaria ...201020363375
new imidazolidinedione derivatives as antimalarial agents.a series of new n-alky- and n-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and rhesus monkey models. new compounds are generally metabolically stable, weakly active in vitro against plasmodium falciparum clones (d6 and w2) and in mice infected with plasmodium berghei sporozoites. representative compounds 8e and 9c showed good causal prophylactic activity in rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by im, delayed pa ...201021282058
a taqman real-time pcr assay for the detection and quantitation of plasmodium knowlesi.the misdiagnosis of plasmodium knowlesi by microscopy has prompted a re-evaluation of the geographic distribution, prevalence and pathogenesis of this species using molecular diagnostic tools. in this report, a specific probe for p. knowlesi, that can be used in a previously described taqman real-time pcr assay for detection of plasmodium spp., and plasmodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium ovale, was designed and validated against clinical samples.201021114872
methylparaben in anopheles gambiae s.l. sugar meals increases longevity and malaria oocyst abundance but is not a preferred diet.the antimicrobial and antifungal chemical methylparaben (methyl-4-hydroxybenzoate) was added to the adult sucrose diet of anopheles gambiae and anopheles arabiensis, and its effect on longevity was determined. in all cases, significant increases in longevity were observed when 0.2% (w/v) methylparaben was added to meals that were refreshed weekly. when fresh sugar diet was refreshed daily, no increase in longevity was observed due to methylparaben suggesting that the effect of methylparaben is t ...200919041323
altered immune responses in rhesus macaques co-infected with siv and plasmodium cynomolgi: an animal model for coincident aids and relapsing malaria.dual epidemics of the malaria parasite plasmodium and hiv-1 in sub-saharan africa and asia present a significant risk for co-infection in these overlapping endemic regions. recent studies of hiv/plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid cd4+ t cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. here, we describe a novel rhesus macaque model for co-infection that supports ...200919774084
orangutans not infected with plasmodium vivax or p. cynomolgi, indonesia.after orangutans in indonesia were reported as infected with plasmodium cynomolgi and p. vivax, we conducted phylogenetic analyses of small subunit ribosomal rna gene sequences of plasmodium spp. we found that these orangutans are not hosts of p. cynomolgi and p. vivax. analysis of >or=1 genes is needed to identify plasmodium spp. infecting orangutans.200919861067
rapid resolution liquid chromatography-mass spectrometry determination of sar97276 in monkey matrices. pharmacokinetics in rhesus monkey infected by plasmodium cynomolgi.since several years, we developed a new class of antimalarial drugs targeting the phospholipid metabolism of the plasmodium falciparum malaria parasite. the bis-thiazolium compound, sar97276, is the lead compound and is now in clinical development. in this paper, we applied the fast rapid resolution liquid chromatography-mass spectrometry technique to the analysis of sar97276 in monkey matrices. the sample pre-treatment procedure involved an acidic precipitation of proteins followed by solid-pha ...200919303732
statistical model to evaluate in vivo activities of antimalarial drugs in a plasmodium cynomolgi-macaque model for plasmodium vivax malaria.preclinical animal models informing antimalarial drug development are scarce. we have used asexual erythrocytic plasmodium cynomolgi infections of rhesus macaques to model plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. using this malaria model, we accumulated data confirming highly reproducible infection patterns, with self-curing parasite peaks reproducibly preceding recrudescence peaks. we applied nonlinear mixed-effect (nlme) models, es ...200919015340
transmission of different strains of plasmodium cynomolgi to aotus nancymaae monkeys and relapse.forty-four splenectomized aotus nancymaae monkeys were infected with 6 different strains of plasmodium cynomolgi, 11 via trophozoites and 33 via sporozoites. sporozoites from anopheles dirus, anopheles freeborni, anopheles gambiae, anopheles maculatus, and anopheles stephensi resulted in prepatent periods ranging from 9 to 39 days (median of 15 days). importantly, relapse was demonstrated in 5 of 5 sporozoite-induced infections with the rossan strain following treatment with chloroquine.200918788885
detection of new babesia microti-like parasites in a rhesus monkey (macaca mulatta) with a suppressed plasmodium cynomolgi infection.a new type of piroplasm, phylogenetically closest to babesia microti-like parasites previously detected in eurasian red squirrels (sciurus vulgaris orientis), was identified in a rhesus monkey (macaca mulatta) imported from china. after challenge with plasmodium cynomolgi m strain blood-stage parasites, the rhesus monkey repeatedly showed markedly reduced levels of plasmodium parasitemia when compared with animals not infected with this organism.200818385363
evidence for strain-specific protective immunity against blood-stage parasites of plasmodium cynomolgi in toque monkey.we have conducted experiments to test the induction of strain-specific protective immunity against plasmodium cynomolgi infections in toque monkeys. plasmodium cynomolgi is closely related biologically and genetically to the human malaria parasite, p. vivax. two groups of monkeys were immunized against either of two strains of p. cynomolgi, namely pcceylon and pc746, by giving two successive drug-cured infections with asexual blood-stage parasites of one or the other strain, 12-weeks apart. to t ...200819067844
cross-reactivity studies of an anti-plasmodium vivax apical membrane antigen 1 monoclonal antibody: binding and structural characterisation.apical membrane antigen 1 (ama1) has an important, but as yet uncharacterised, role in host cell invasion by the malaria parasite, plasmodium. the protein, which is quite conserved between plasmodium species, comprises an ectoplasmic region, a single transmembrane segment and a small cytoplasmic domain. the ectoplasmic region, which can induce protective immunity in animal models of human malaria, is a leading vaccine candidate that has entered clinical trials. the monoclonal antibody f8.12.19, ...200717229439
biochemical and immunological characterization of e. coli expressed 42 kda fragment of plasmodium vivax and p. cynomolgi bastianelli merozoite surface protein-1.plasmodium vivax is one of the most widely distributed human malaria parasites and due to drug-resistant strains, its incidence and prevalence has increased, thus an effective vaccine against the parasites is urgently needed. one of the major constraints in developing p. vivax vaccine is the lack of suitable in vivo models for testing the protective efficacy of the vaccine. p. vivax and p. cynomolgi bastianelli are the two closely related malaria parasites and share a similar clinical course of ...200718320841
synthesis and antimalarial activity of new 1,12-bis(n,n'-acetamidinyl)dodecane derivatives.amidoxime and o-substituted derivatives of the bis-alkylamidine 1,12-bis(n,n'-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. the bis-o-methylsulfonylamidoxime 8 and the bis-oxadiazolone 9 derivatives show relatively potent antimalarial activity after oral administration.200717123818
new adamantane-based spiro 1,2,4-trioxanes orally effective against rodent and simian malaria.new 6-arylvinyl- and 6-adamantylvinyl-substituted 1,2,4-trioxanes (13a-g and 14a,b) have been prepared and evaluated for antimalarial activity against multidrug resistant plasmodium yoelii nigeriensis in mice by both oral and intramuscular routes. while all the 6-arylvinyl-substituted trioxanes, 13a-f, showed promising activity, none of the 6-adamantylvinyl-substituted trioxanes, 13g and 14a,b, exhibited significant activity. trioxane, 13f, the most active compound of the series, provided 100% a ...200717266204
recent independent evolution of msp1 polymorphism in plasmodium vivax and related simian malaria parasites.the plasmodium msp-1 is a promising malaria vaccine candidate. however, the highly polymorphic nature of the msp-1 gene (msp1) presents a potential obstacle for effective vaccine development. to investigate the evolutionary history of msp1 polymorphism in p. vivax, we construct phylogenetic trees of msp1 from p. vivax and related monkey malaria parasite species. all p. vivax msp1 alleles cluster in the p. vivax lineage and are not distributed among other species. similarly, all p. cynomolgi msp1 ...200717706800
oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation.early gestational malaria is more deleterious than late gestational infection. still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities.200717722865
malaria causal prophylactic activity of imidazolidinedione derivatives.a series of acid-stable carboxamide derivatives of 2-guanidinoimidazolidinedione (5a-c and 6a-c) were prepared as potential malaria prophylactic and radical cure agents. the new compounds showed moderate to good causal prophylactic activity in mice infected with plasmodium yoelii sporozoites. three compounds were further tested for causal prophylactic activity in rhesus monkeys infected with plasmodium cynomolgi sporozoites, and all showed a delay in patency from 13 to 40 days at 30 mg/kg/day x ...200717967003
8-(1-naphthalen-2-yl-vinyl)-6,7,10-trioxaspiro (4.5) decane, a new 1,2,4-trioxane effective against rodent and simian malaria.a new series of 8-(1-aryl-vinyl)-6,7,10-trioxaspiro [4.5] decanes 7a-e and 3-(1-aryl-vinyl)-l,2,5-trioxaspiro [5.5] undecanes 8a-e have been prepared and screened against multi-drug resistant plasmodium yoelii in mice. 8-(1-naphthalen-2-yl-vinyl)-6,7,10-trioxaspiro [4.5] decane 7b, the most active trioxane of the series, has also shown promising activity against plasmodium cynomolgi in rhesus monkeys.200616275088
observations on the exoerythrocytic stages of different isolates of plasmodium cynomolgi in hepatocytes of new world aotus and saimiri monkeys.sporozoites of 3 isolates of plasmodium cynomolgi dissected from the salivary glands of anopheles dirus and anopheles quadrimaculatus were injected intravenously into 9 new world monkeys. liver stage parasites were demonstrated in all 9 animals; 7 of these animals also produced blood stages after prepatent periods of 9 to 23 days.200616629341
[molecular identification of naturally acquired plasmodium knowlesi infection in a human case].to confirm the diagnosis of a human case with atypical vivax-malaria from yunnan province by molecular technique.200617094597
structure identification and prophylactic antimalarial efficacy of 2-guanidinoimidazolidinedione derivatives.the reported synthetic procedure of wr182393, a 2-guanidinoimidazolidinedione derivative with high prophylactic antimalarial activity, was found to be a mixture of three closely related products. poor solubility of wr182393 in both water and organic solvents and its impractical synthetic method have made the purification and structure identification of the reaction mixture a highly challenging task. the problems were circumvented by prodrug approach involving carbamate formation of the mixture, ...200515653337
the reticulocyte binding proteins of plasmodium cynomolgi: a model system for studies of p. vivax. 200515990180
plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound cdri 80/53 (elubaquine) in rhesus monkeys.the gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound cdri 80/53, bulaquine), has been evaluated against plasmodium cynomolgi b in rhesus monkeys. colony bred anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. complete loss of oocyst development and mosquito infectivity was observed within 24 h after ...200516005457
merozoite surface protein 1 of plasmodium vivax induces a protective response against plasmodium cynomolgi challenge in rhesus monkeys.the 42-kda fragment of the merozoite surface protein 1 (msp-1(42)) is a leading candidate for the development of a vaccine to control malaria. we previously reported a method for the production of plasmodium vivax msp-1(42) (pvmsp-1(42)) as a soluble protein (s. dutta, l. w. ware, a. barbosa, c. f. ockenhouse, and d. e. lanar, infect. immun. 69:5464-5470, 2001). we report here a process to manufacture the same pvmsp-1(42) protein but as an insoluble inclusion body-derived protein which was then ...200516113314
hydrolytic enzyme activity in rhesus monkey placenta during early gestational malaria: histochemical studies.early gestational malaria is found to be more fatal than late gestational infection but the pathophysiology of early gestational placenta, the maternofoetal organ responsible for maintenance of pregnancy, remains unexplored. present study dealing with hydrolytic enzymes in early gestational placenta of rhesus monkeys during plasmodium cynomolgi infection was anticipated to provide a better insight into the functional impairment of this organ during early gestational maternal malaria.200516457382
studies on two strains of plasmodium cynomolgi in new world and old world monkeys and mosquitoes.infections that cause the gombak and smithsonian strains of plasmodium cynomolgi were induced in macaca mulatta, aotus lemurinus griseimembra, aotus nancymai, and saimiri boliviensis monkeys. transmission of the gombak strain to aotus spp. monkeys was obtained by the injection of sporozoites dissected from the salivary glands of experimentally infected anopheles dirus and by the bites of infected an. dirus and anopheles farauti mosquitoes. two s. boliviensis monkeys were infected via the injecti ...200515986601
transcriptome profiles of host gene expression in a monkey model of human malaria.we used human microarrays to examine gene expression in a rhesus monkey model of human plasmodium vivax malaria (p. cynomolgi in macaca mulatta). whole-blood cells were collected for extraction of rna before infection, during both the initial liver phase of infection and bloodstream infection, and during the course of 2 bloodstream relapses. clustering analysis showed that similarities in gene expression were greater at similar stages of the protocol for the 2 different monkeys than for the same ...200415633100
[induction of protective immunity in rhesus monkey by inoculation with recombinant fusion protein of cholera toxin b subunit-multivalent epitopes of plasmodium falciparum].rhesus monkeys (5 in each group) were inoculated with recombinant fusion protein of cholera toxin b subunit and multi-valent epitopes of plasmodium falciparum intranasal or intramuscular (i.m.). immune-responses and protective effect were evaluated. the antibody titer (geometry mean) against ctb reached 1:512 (intranasal) and 1:10000 (i.m.) 14 day after 3rd immunization, and antibodies against p. falciparum were also elucidated, the titers in i.m. group were also significantly higher than that i ...200415968980
prodrugs of bisthiazolium salts are orally potent antimalarials.we created neutral antimalarial prodrugs that deliver bisthiazolium compounds with antimalarial activity in the nanomolar range. these drugs primarily affect early intraerythrocytic stages through rapid, nonreversible cytotoxicity. the compounds are suitable for both parenteral and oral use and plasma promotes rapid conversion of the prodrug into the drug. we demonstrate that very low doses offer protection in a murine model of malaria. the drugs show great potential for curing high parasitemia ...200415492221
replication fork-stimulated eif-4a from plasmodium cynomolgi unwinds dna in the 3' to 5' direction and is inhibited by dna-interacting compounds.plasmodium cynomolgi dead-box dna helicase 45 (pcddh45) is an atp-dependent dna-unwinding enzyme with intrinsic dna-dependent atpase activity and is highly homologous to eif-4a. in this study, we have further characterized and tested the effect of various dna-interacting compounds on the dna-unwinding activity of pcddh45. the results show that pcddh45 translocates in the 3' to 5' direction along the bound strand, a replication fork-like structure of the substrate stimulates its dna-unwinding act ...200312745261
blood schizontocidal activity of wr 238605 (tafenoquine) against plasmodium cynomolgi and plasmodium fragile infections in rhesus monkeys.a new 8-aminoquinoline antimalarial wr 238605 (tafenoquine), developed initially as a primaquine alternative for prevention of plasmodium vivax relapses was evaluated for blood schizontocidal activity against two simian malaria infections namely plasmodium cynomolgi b and plasmodium fragile in rhesus monkeys. treatment with wr 238605 at a dose of 3.16 mg(base)/kg/day x 7 days cured established trophozoite induced infections in monkeys with both these parasites. the lower dose of 1.00 mg/kg/day c ...200312711101
the development of exoerythrocytic stages of plasmodium inui shortti in new world monkeys.attempts are being made to adapt old world monkey malarial parasites to new world monkeys for vaccine and molecular studies. several of these (plasmodium cynomolgi berok, plasmodium fragile, and plasmodium knowlesi) grow readily but have failed to produce infective gametocytes. plasmodium gonderi and plasmodium fieldi develop in the liver after sporozoite inoculation but have failed to establish infection in the erythrocyte. anopheles dirus mosquitoes infected with plasmodium inui shortti by fee ...200312880277
quantitative trait loci in anopheles gambiae controlling the encapsulation response against plasmodium cynomolgi ceylon.anopheles gambiae females are the world's most successful vectors of human malaria. however, a fraction of these mosquitoes is refractory to plasmodium development. l3-5, a laboratory selected refractory strain, encapsulates transforming ookinetes/early oocysts of a wide variety of plasmodium species. previous studies on these mosquitoes showed that one major (pen1) and two minor (pen2, pen3) autosomal dominant quantitative trait loci (qtls) control the melanotic encapsulation response against p ...200314577840
dna prime-protein boost immunization in monkeys: efficacy of a novel construct containing functional domains of plasmodium cynomolgi cs and trap.we report the efficacy of a bimodal immunization regimen that involved priming with naked dna (multiple doses) followed by a booster with recombinant protein in rhesus monkeys with a chimeric construct containing the n-terminus of thrombospondin-related adhesive protein and the c-terminus of circumsporozoite protein of plasmodium cynomolgi. the vaccinated animals developed high titer antibodies against the chimeric antigen, the two components of the hybrid and the native proteins of sporozoites. ...200314642309
isolation and characterization of an eif-4a homologue from plasmodium cynomolgi. 200212387853
a class of potent antimalarials and their specific accumulation in infected erythrocytes.during asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. this activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. we found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. the lead compound, g25, potently inhibited in vitro growth of the human malaria parasites plasmodium falciparum and p. vivax and was 1000-fold less toxic to m ...200211847346
cytokine responses during acute simian plasmodium cynomolgi and plasmodium knowlesi infections.experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. plasmodium cynomolgi (p. vivax-like) and p. knowlesi (p. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. this study analyzed cytokine gene expression (interleukin-12, ...200212518848
immunogenicity and protective efficacy of three dna vaccines encoding pre-erythrocytic- and erythrocytic-stage antigens of plasmodium cynomolgi in rhesus monkeys.although several malaria vaccine candidate antigens have been identified, the most suitable methods for their delivery are still being investigated. in this regard, direct immunization with dna encoding these vaccine target antigens is an attractive alternative. here, we have investigated the immune responses to dna immunization with three major vaccine target antigens: the apical membrane antigen-1 and the 19-kda c-terminal fragment of merozoite surface protein-1 from the erythrocytic stage, an ...200212208604
merozoite surface protein-9 of plasmodium vivax and related simian malaria parasites is orthologous to p101/abra of p. falciparum.plasmodium vivax merozoite surface protein-9 (pvmsp-9) is characterized here along with orthologues from the related simian malarias plasmodium cynomolgi and plasmodium knowlesi. we show that although the corresponding msp-9 proteins do not have acidic-basic repeated amino acid (aa) motifs, they are related to the plasmodium falciparum acidic-basic repeat antigen (abra) also known as p101. recognition of this new interspecies plasmodium msp family stems from the prior identification of related m ...200211849704
[practicability of ifat using plasmodium cynomolgi and plasmodium falciparum antigens in different malarious areas].to compare the practicability of ifat in different malarious areas using plasmodium cynomolgi(p.c.) and plasmodium falciparum(p.f.) antigens.200012567477
azithromycin: antimalarial profile against blood- and sporozoite-induced infections in mice and monkeys.the spectrum of antimalarial activity of the new macrolide antibiotic azithromycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of plasmodium yoelii nigeriensis (n-67) in swiss mice and with simian parasite plasmodium cynomolgi b in rhesus monkeys. against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally from day 0 to day 3 or from day 2 to day 5 to mice ...200010631075
demonstration of a persisting exo-erythrocytic cycle in plasmodium cynomolgi and its bearing on the production of relapses. 1948. 200011196492
plasmodium cynomolgi: transfection of blood-stage parasites using heterologous dna constructs. 199910464040
high-level expression of plasmodium vivax apical membrane antigen 1 (ama-1) in pichia pastoris: strong immunogenicity in macaca mulatta immunized with p. vivax ama-1 and adjuvant sbas2.the apical membrane antigen 1 (ama-1) family is a promising family of malaria blood-stage vaccine candidates that have induced protection in rodent and nonhuman primate models of malaria. correct conformation of the protein appears to be essential for the induction of parasite-inhibitory responses, and these responses appear to be primarily antibody mediated. here we describe for the first time high-level secreted expression (over 50 mg/liter) of the plasmodium vivax ama-1 (pv66/ama-1) ectodomai ...19999864194
the crystal structure of c-terminal merozoite surface protein 1 at 1.8 a resolution, a highly protective malaria vaccine candidate.the c-terminal proteolytic processing product of merozoite surface protein 1 (msp1) appears essential for successful erythrocyte invasion by the malarial parasite, plasmodium. we have determined the crystal structure at 1.8 a resolution of a soluble baculovirus-recombinant form of the protein from p. cynomolgi, which confers excellent protective efficacy in primate vaccination trials. the structure comprises two egf-like domains, and sequence comparisons strongly suggest that the same conformati ...199910230398
linkage of a gene causing malaria refractoriness to diphenol oxidase-a2 on chromosome 3 of anopheles gambiae.an inbred line of the african malaria vector anopheles gambiae is refractory to development of malaria parasites. it is homozygous for a 4.3-kb sal i restriction fragment at the dox-a2 locus, whereas the parent population is polymorphic at this locus, and a susceptible line is homozygous for an alternate 3.85-kb fragment. the dox-a2 locus is located in the middle of chromosome 3r, in division 33b, and is tightly linked to a cluster of genes including dopa decarboxylase that are involved in the p ...19999988317
rna helicase-related genes of plasmodium falciparum and plasmodium cynomolgi.rna helicases play many essential roles including cell development and growth. using degenerate oligonucleotide primers designed to amplify dna fragments flanked by the highly conserved helicase motifs vldead and yihrig and genomic dnas from the malarial parasites as a template, we have cloned two putative rna helicase genes (546 and 540 bp) from p. falciparum and one gene (546 bp) from p. cynomologi. southern blot analysis revealed that these could be multiple and single-copy genes in p. falcip ...199910049705
plasmodium vivax, p. cynomolgi, and p. knowlesi: identification of homologue proteins associated with the surface of merozoites.we have identified a plasmodium vivax merozoite surface protein (msp) that migrates on sds-polyacrylamide gels at a mr of about 185 kda. this protein was recognized by a p. vivax monoclonal antibody (mab) that localizes the protein by immunofluorescence to the surface of merozoites and also immunoprecipitates this protein from np-40 detergent extracts of [35s]methionine metabolically radiolabeled p. vivax schizonts. the p. vivax msp does not become biosynthetically radiolabeled with [3h]glucoami ...199910072326
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