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Malarial Parasite (malarial + parasite)
Selected AbstractsChloroquine resistance in the malarial parasite, Plasmodium falciparumMEDICINAL RESEARCH REVIEWS, Issue 5 2002Lyann M.B. Ursos Abstract Malarial parasites remain a health problem of staggering proportions. Worldwide, they infect about 500 million, incapacitate tens of millions, and kill approximately 2.5 million (mostly children) annually. Four species infect humans, but most deaths are caused by one particular species, Plasmodium falciparum. The rising number of malarial deaths is due in part to increased drug resistance in P. falciparum. There are many varieties of antimalarial drug resistance, and there may very well be several molecular level contributions to each variety. This is because there are a number of different drugs with different mechanisms of action in use, and more than one molecular event may sometimes be relevant for resistance to any one class of drugs. Thus, "multidrug" resistance in a clinical setting likely entails complex combinations of overlapping resistance pathways, each specific for one class of drug, that then add together to confer the particular multidrug resistance phenotype. Nonetheless, rapid progress has been made in recent years in elucidating mechanisms of resistance to specific classes of antimalarial drugs. As one example, resistance to the antimalarial drug chloroquine, which has been the mainstay therapy for decades, is becoming well understood. This article focuses on recent advances in determining the molecular mechanism of chloroquine resistance, with particular attention to the biochemistry and biophysics of the P. falciparum digestive vacuole, wherein changes in pH have recently been found to be associated with chloroquine resistance. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 465,491, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10016 [source] cDNA cloning, functional expression and characterization of kynurenine 3-hydroxylase of Anopheles stephensi (Diptera: Culicidae)INSECT MOLECULAR BIOLOGY, Issue 5 2002M. Hirai Abstract Kynurenine 3-hydroxylase (K3H) is a NADPH-dependent flavin monooxygenase involved in the tryptophan pathway. Xanthurenic acid (XA) is a metabolite of this pathway and has recently been identified as a gamete activating factor (GAF) of the malarial parasite. We cloned K3H cDNA from Anopheles stephensi (AsK3H), because anopheline mosquitoes are a vector of the human malaria parasite, Plasmodium falciparum and the catalytic function of AsK3H in XA production. Recombinant AsK3H protein was expressed in Sf-9 cells using the baculovirus system and its enzymatic properties were characterized. The specific activities of crude cell lysate and affinity purified protein were 94.9 ± 6.2 and 865.6 ± 10.5 nmol/min/mg protein, respectively. The optimum pH of AsK3H was 7.0. Analysis of AsK3H gene expression using RT-PCR revealed that AsK3H was constitutively expressed in egg, larva, pupa and adult. [source] Chloroquine resistance in the malarial parasite, Plasmodium falciparumMEDICINAL RESEARCH REVIEWS, Issue 5 2002Lyann M.B. Ursos Abstract Malarial parasites remain a health problem of staggering proportions. Worldwide, they infect about 500 million, incapacitate tens of millions, and kill approximately 2.5 million (mostly children) annually. Four species infect humans, but most deaths are caused by one particular species, Plasmodium falciparum. The rising number of malarial deaths is due in part to increased drug resistance in P. falciparum. There are many varieties of antimalarial drug resistance, and there may very well be several molecular level contributions to each variety. This is because there are a number of different drugs with different mechanisms of action in use, and more than one molecular event may sometimes be relevant for resistance to any one class of drugs. Thus, "multidrug" resistance in a clinical setting likely entails complex combinations of overlapping resistance pathways, each specific for one class of drug, that then add together to confer the particular multidrug resistance phenotype. Nonetheless, rapid progress has been made in recent years in elucidating mechanisms of resistance to specific classes of antimalarial drugs. As one example, resistance to the antimalarial drug chloroquine, which has been the mainstay therapy for decades, is becoming well understood. This article focuses on recent advances in determining the molecular mechanism of chloroquine resistance, with particular attention to the biochemistry and biophysics of the P. falciparum digestive vacuole, wherein changes in pH have recently been found to be associated with chloroquine resistance. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 465,491, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10016 [source] Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable deliveryPLANT BIOTECHNOLOGY JOURNAL, Issue 2 2010Abdoreza Davoodi-Semiromi Summary Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin-B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen-1 (AMA1) and merozoite surface protein-1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB-AMA1 and CTB-MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce, respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen-specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross-reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB-specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin-10+ T cell but not Foxp3+ regulatory T cells, suppression of interferon-, and absence of interleukin-17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast-derived vaccine antigens for long-term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity. [source] Molecular interactions between Plasmodium and its insect vectorsCELLULAR MICROBIOLOGY, Issue 11 2002R. E. Sinden Summary Our understanding of the intricate interactions between the malarial parasite and the mosquito vector is complicated both by the number and diversity of parasite and vector species, and by the experimental inaccessibility of phenomena under investigation. Steady developments in techniques to study the parasite in the mosquito have recently been augmented by methods to culture in their entirety the sporogonic stages of some parasite species. These, together with the new saturation technologies, and genetic transformation of both parasite and vector will permit penetrating studies into an exciting and largely unknown area of parasite,host interactions, an understanding of which must result in the development of new intervention strategies. This microreview highlights key areas of current basic molecular interest, and identifies numerous lacunae in our knowledge that must be filled if we are to make rational decisions for future control strategies. It will conclude by trying to explain why in the opinion of this reviewer understanding malaria,mosquito interactions may be critical to our future attempts to limit a disease of growing global importance. [source] Surveillance of vivax malaria vectors and civilian patients for malaria high-risk areas in northern Gyeonggi and Gangwon Provinces near the demilitarized zone, Republic of Korea, 2003,2006ENTOMOLOGICAL RESEARCH, Issue 4 2010Jae Chul SHIM Abstract After re-emergence of malaria in 1993, a continued increase in Plasmodium vivax cases was observed from 1993 to 2006 in northern Gyeonggi and Gangwon Provinces adjacent to the demilitarized zone separating North from South Korea. Annual parasite incidence per 1000 people ranged from 0.33 in 2004 to 0.89 in 2006. While malaria case rates declined (22.6%) in 2004, they increased 75.1% in 2005 and 51.7% in 2006 from the previous years. An initial incorrect diagnosis of 46.8% of malaria cases as common cold resulted in a mean delay of 1.3 days for the detection malarial parasites. Of the total cases, 10.2% from December to May were due to latent intrinsic incubation infections acquired the previous malaria season and the rest of the cases from June to November were either latent or short incubation infections. Overall, the peak anopheline population occurred from July to September, resulting in a similar peak in malaria cases. While malaria cases increased during 2005,2006, anopheline populations, based on trap indices, were not significantly different during 4 years of surveillance. To decrease the malaria patient infective period to mosquitoes, public health centers in Paju and Cheorwon in 2006 prescribed chloroquine + primaquine at days 0,3 after initial malaria diagnosis followed by an additional 11 days of primaquine (early primaquine treatment), rather than chloroquine on days 0,3 and primaquine on days 4,17 (delayed primaquine treatment). A reduction in the malaria parasite incidence during 2007 was recorded for the two locations offering the early primaquine treatment relative to other locations using the delayed primaquine treatment. [source] Carotenoid and melanin-based ornaments signal similar aspects of male quality in two populations of the common yellowthroatFUNCTIONAL ECOLOGY, Issue 1 2010Peter O. Dunn Summary 1.,Female preferences for particular male ornaments may shift between populations as a consequence of ecological differences that change the reliability and detectability of the ornament, but few studies have examined how ornaments function in different populations. 2.,We examined the signalling function of male plumage ornaments in a warbler, the common yellowthroat (Geothlypis trichas), breeding in New York (NY) and Wisconsin (WI), USA. Males have two prominent ornaments: a black facial mask pigmented with melanin and a yellow bib pigmented by carotenoids. Previous studies in WI indicate that the size of the mask, and not the bib, is primarily related to female choice and male reproductive success. In NY, however, the pattern is reversed and attributes of the bib (size and colour), and not the mask, are the target of sexual selection. 3.,We found that brightness of the yellow bib was the best signal of humoral immunity (immunoglobulin G) in NY and mask size was the best signal in WI, after controlling for breeding experience and capture date. Thus, similar aspects of male quality appeared to be signalled by different ornaments in different populations. 4.,There was no difference between populations in the level of plasma carotenoids or the prevalence of malarial parasites, which may affect the costs and benefits of choosing males with particular ornaments in each location. 5.,Even though females in different populations prefer different ornaments produced by different types of pigments, these ornaments appear to be signalling similar aspects of male quality. Our results caution against inferring the function of particular ornaments based simply on their type of pigment. [source] A glimpse into the clinical proteome of human malaria parasites Plasmodium falciparum and Plasmodium vivaxPROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2009Pragyan Acharya Abstract Malaria causes a worldwide annual mortality of about a million people. Rapidly evolving drug-resistant species of the parasite have created a pressing need for the identification of new drug targets and vaccine candidates. By developing fractionation protocols to enrich parasites from low-parasitemia patient samples, we have carried out the first ever proteomics analysis of clinical isolates of early stages of Plasmodium falciparum (Pf) and P. vivax. Patient-derived malarial parasites were directly processed and analyzed using shotgun proteomics approach using high-sensitivity MS for protein identification. Our study revealed about 100 parasite-coded gene products that included many known drug targets such as Pf hypoxanthine guanine phosphoribosyl transferase, Pf L -lactate dehydrogenase, and Plasmepsins. In addition, our study reports the expression of several parasite proteins in clinical ring stages that have never been reported in the ring stages of the laboratory-cultivated parasite strain. This proof-of-principle study represents a noteworthy step forward in our understanding of pathways elaborated by the parasite within the malaria patient and will pave the way towards identification of new drug and vaccine targets that can aid malaria therapy. [source] Liver invasion by malarial parasites , how do malarial parasites break through the host barrier?CELLULAR MICROBIOLOGY, Issue 12 2004Masao Yuda Summary Malarial transmission to the human host is established by sporozoite infection of the liver. Sporozoites are released from the mosquito salivary glands and carried by the blood flow to the liver sinusoid. In the sinusoid, sporozoites leave the blood circulation by crossing the sinusoidal cell layer to infect hepatocytes, the site for their development into the erythrocyte-invasive forms. Traversal of the sinusoidal cell layer and subsequent hepatocyte infection are the most important events in sporozoite liver invasion, but the molecular basis of both events remains to be elucidated. The present review of sporozoite liver invasion focuses on recent advances in this topic obtained by application of reverse genetics. Sporozoites traverse host cells, rupturing the host cell membrane in the process. Three microneme proteins have important roles in this motility. Disruption of one of these genes abolishes or severely impairs cell traversal without affecting other types of invasive motility. Studies using these disruptant parasites indicate that cell-traversal ability is required for crossing the sinusoidal cell layer and accessing the hepatocytes for infection. This process is homologous to midgut epithelium penetration by the malarial ookinete, because identical or paralogous genes are critically involved in both processes. After arrival at the hepatocyte, the invasion mode of the sporozoites switches from cell traversal to hepatocyte infection. [source] | ||||||||||