Academic literature on the topic 'Malaria virulence'
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Journal articles on the topic "Malaria virulence"
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Lin, Jing-wen, Adam J. Reid, Deirdre Cunningham, Ulrike Böhme, Irene Tumwine, Sara Keller-Mclaughlin, Mandy Sanders, Matthew Berriman, and Jean Langhorne. "Genomic and transcriptomic comparisons of closely related malaria parasites differing in virulence and sequestration pattern." Wellcome Open Research 3 (November 2, 2018): 142. http://dx.doi.org/10.12688/wellcomeopenres.14797.1.
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Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. However, despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.
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Lin, Jing-wen, Adam J. Reid, Deirdre Cunningham, Ulrike Böhme, Irene Tumwine, Sara Keller-Mclaughlin, Mandy Sanders, Matthew Berriman, and Jean Langhorne. "Genomic and transcriptomic comparisons of closely related malaria parasites differing in virulence and sequestration pattern." Wellcome Open Research 3 (December 6, 2018): 142. http://dx.doi.org/10.12688/wellcomeopenres.14797.2.
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Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. Despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.
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Deitsch, Kirk W. "Malaria Virulence Genes." Cell 121, no. 1 (April 2005): 1–2. http://dx.doi.org/10.1016/j.cell.2005.03.019.
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Schneider, Petra, Andrew S. Bell, Derek G. Sim, Aidan J. O'Donnell, Simon Blanford, Krijn P. Paaijmans, Andrew F. Read, and Sarah E. Reece. "Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi." Proceedings of the Royal Society B: Biological Sciences 279, no. 1747 (September 26, 2012): 4677–85. http://dx.doi.org/10.1098/rspb.2012.1792.
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Here, we test the hypothesis that virulent malaria parasites are less susceptible to drug treatment than less virulent parasites. If true, drug treatment might promote the evolution of more virulent parasites (defined here as those doing more harm to hosts). Drug-resistance mechanisms that protect parasites through interactions with drug molecules at the sub-cellular level are well known. However, parasite phenotypes associated with virulence might also help parasites survive in the presence of drugs. For example, rapidly replicating parasites might be better able to recover in the host if drug treatment fails to eliminate parasites. We quantified the effects of drug treatment on the in-host survival and between-host transmission of rodent malaria ( Plasmodium chabaudi ) parasites which differed in virulence and had never been previously exposed to drugs. In all our treatment regimens and in single- and mixed-genotype infections, virulent parasites were less sensitive to pyrimethamine and artemisinin, the two antimalarial drugs we tested. Virulent parasites also achieved disproportionately greater transmission when exposed to pyrimethamine. Overall, our data suggest that drug treatment can select for more virulent parasites. Drugs targeting transmission stages (such as artemisinin) may minimize the evolutionary advantage of virulence in drug-treated infections.
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Penman, Bridget, and Sunetra Gupta. "Evolution of virulence in malaria." Journal of Biology 7, no. 6 (2008): 22. http://dx.doi.org/10.1186/jbiol83.
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Mackinnon, Margaret J., and Andrew F. Read. "Virulence in malaria: an evolutionary viewpoint." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 359, no. 1446 (June 29, 2004): 965–86. http://dx.doi.org/10.1098/rstb.2003.1414.
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Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi , and field data on the human malaria parasite, P. falciparum , in relation to this virulence trade–off hypothesis . The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade–off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs.
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Metcalf, C. J. E., G. H. Long, N. Mideo, J. D. Forester, O. N. Bjørnstad, and A. L. Graham. "Revealing mechanisms underlying variation in malaria virulence: effective propagation and host control of uninfected red blood cell supply." Journal of The Royal Society Interface 9, no. 76 (June 20, 2012): 2804–13. http://dx.doi.org/10.1098/rsif.2012.0340.
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Malaria parasite clones with the highest transmission rates to mosquitoes also tend to induce the most severe fitness consequences (or virulence) in mammals. This is in accord with expectations from the virulence–transmission trade-off hypothesis. However, the mechanisms underlying how different clones cause virulence are not well understood. Here, using data from eight murine malaria clones, we apply recently developed statistical methods to infer differences in clone characteristics, including induction of differing host-mediated changes in red blood cell (RBC) supply. Our results indicate that the within-host mechanisms underlying similar levels of virulence are variable and that killing of uninfected RBCs by immune effectors and/or retention of RBCs in the spleen may ultimately reduce virulence. Furthermore, the correlation between clone virulence and the degree of host-induced mortality of uninfected RBCs indicates that hosts increasingly restrict their RBC supply with increasing intrinsic virulence of the clone with which they are infected. Our results demonstrate a role for self-harm in self-defence for hosts and highlight the diversity and modes of virulence of malaria.
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Nunes-Alves, Cláudio. "Linking virulence and transmission in malaria." Nature Reviews Microbiology 12, no. 10 (September 8, 2014): 655. http://dx.doi.org/10.1038/nrmicro3354.
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Mancio-Silva, Liliana, Ksenija Slavic, Margarida T. Grilo Ruivo, Ana Rita Grosso, Katarzyna K. Modrzynska, Iset Medina Vera, Joana Sales-Dias, et al. "Nutrient sensing modulates malaria parasite virulence." Nature 547, no. 7662 (July 2017): 213–16. http://dx.doi.org/10.1038/nature23009.
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Chookajorn, Thanat, Ron Dzikowski, Matthias Frank, Felomena Li, Alisha Z. Jiwani, Daniel L. Hartl, and Kirk W. Deitsch. "Epigenetic memory at malaria virulence genes." Proceedings of the National Academy of Sciences 104, no. 3 (January 5, 2007): 899–902. http://dx.doi.org/10.1073/pnas.0609084103.
Full textDissertations / Theses on the topic "Malaria virulence"
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Long, Gráinne Helen. "Immunopathology and virulence evolution in rodent malaria." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/1962.
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From an evolutionary perspective, natural selection is expected to maximize transmission to new hosts. If a live, mobile host often benefits parasite transmission, the question arises as to why malaria parasites are virulent? The favoured trade-off view of virulence evolution assumes that virulence arises as an unavoidable consequence of parasite resource exploitation within the host that is necessary to maximise parasite transmission. However, virulence is not always a simple function of parasite density and can arise as a result of immune-mediated virulence (immunopathology). This thesis explores how immunopathology contributes to virulence on the one hand, and parasite transmission on the other, in order to improve our understanding of parasite virulence evolution. In tackling this question, the role parasite genetic diversity plays in determining immunopathology induced during malaria infection was also addressed. Using the rodent malaria Plasmodium chabaudi chabaudi (P.c.c.) in C57BL/6 mice, I explored whether immune factors – in terms of specific host cytokines central to the protection-pathology balancing act of the immune response elicited against malaria parasites – help to determine the virulence induced during infection with genetically distinct parasites, and if so, what effect this may have on transmission-stage parasites. I showed that the cytokine milieu induced by P.c.c. parasites during primary infection varies with parasite genotype and that virulence can arise independent of parasite density, via immunopathology. Specifically, I showed propensity to induce the pro-inflammatory cytokine tumour necrosis factor [TNF]-a contributes to the virulence induced, regardless of P.c.c. clone. Importantly, I also showed that across P.c.c. genotype, TNF-a reduces the density of transmission-stage parasites. Thus, virulence is not always a simple function of parasite replication, having an immune-mediated component which acts to reduce transmission potential. The importance of parasite genotype in determining the degree of immunopathological virulence induced during malaria infection was revealed by studying the anti-inflammatory arm of the immune response. The extent to which the anti-inflammatory cytokines interleukin [IL]-10 or transforming growth factor [TGF]-b limited the immunopathology induced during P.c.c. infection depended on parasite clone. In addition, parasite genotype played a key role in determining how such anti-inflammatory manipulations affected the density of transmission-stage parasites; being detrimental, beneficial or incidental to parasite fitness, depending on P.c.c. clone. Although the general mechanisms of immune regulation are qualitatively unchanged across distinct P.c.c. clones, these data emphasize the importance of parasite genotype: distinct clones differ quantitatively in immune regulation, which contributes towards their distinct virulence and fitness schedules. Overall, I found that even within a parasite species – in this case P. chabaudi – the effect of immunopathology on the virulence-transmissibility relationship may be genetically variable and may not conform to that predicted by the trade-off hypothesis, having the potential to alter the costs and benefits of virulence, depending on parasite genotype. Thus, the host immune response may play a role shaping virulence evolution and defining the limit to malaria virulence in nature.
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Pettersson, Fredrik. "Sequestration, virulence and future interventions in Plasmodium falciparum malaria." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-568-2/.
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Heddini, Andreas. "Endothelial cytoadherence, rosetting and virulence in Plasmodium falciparum malaria /." Stockholm : [Karolinska institutets bibl.], 2001.
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Timms, Rebecca. "The ecology and evolution of virulence in mixed infections of malaria parasites." Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/13132.
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This thesis focuses on the determinants of virulence in single and mixed-clone malaria infections, and the consequent impact of these infections for host- and parasite-fitness. Controlled experiments were conducted using a rodent model of malarial disease, Plasmodium chabaudi. Mice were infected with precise numbers of virulent and avirulent parasites. In the mixtures, known ratios of two clones that differed in virulence were used. Virulence was quantified in terms of host morbidity and mortality. Experiments investigating how virulence is determined in mixtures revealed that both the proportion of virulent clone in the innocula, and the genetic diversity of the infection determine virulence. Replacing virulent parasites with avirulent ones in a mixture was shown to confer protection for the host. These results challenge the various assumptions made in the models of the evolution of virulence about how virulence is determined in mixtures. They also suggest that selection against virulence can be reduced if virulent clones coinfect with avirulent ones, because host mortality is reduced in mixtures when the avirulent clone dominates. In single infections, the inoculating dose of virulent and avirulent parasites affected the virulence of the infection. Larger doses caused greater anaemia. They also caused additional weight loss, and death, but only for the virulent clone. Clone differences in virulence were maintained over the range of doses. Dose effects were manifested through the timing and/or magnitude of peak parasite densities, broadly supporting the idea that disease severity is due to the time the host has to control parasite densities and ameliorate the effects of parasites. To investigate the correlates of mortality, multivariate analyses were conducted. These generally showed that both the initial weight and red blood cell density of mice, and the rate at which they lost red blood cells and weight affected their probability of survival.
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Ferguson, Heather M. "The ecology and evolutionary implications of malaria parasite virulence in mosquito vectors." Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/14838.
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A laboratory study with the rodent malaria parasite P. chabaudi and A. stephensi vector indicated that mosquito morality varied with parasite genotype, infection diversity and nutrient availability. In standard conditions, mixed clone infections were the most lethal, but when glucose water was limited, mortality was highest in mosquitoes infected with CR. A second experiment showed that under standard conditions, mixed infections also had the greatest impact on vector fecundity. The virulence of mixed infections could not be explained by parasite load, nor their rate of resource uptake by parasites within the mosquitoes. During the parasite development period, infected mosquitoes had the same amount of three key physiological resources (lipids, glycogen, proteins), as those that were uninfected. Furthermore, mosquitoes infected with the most virulent parasite genotypes had an increased abundance of glucose relative to the controls. This is consistent with Plasmodium manipulating mosquito sugar-feeding behaviour in order to increase its own transmission. Several laboratory studies of malaria parasites and some field observations suggest that Plasmodium virulence in vertebrates is positively correlated with transmission to mosquitoes. A final experiment was undertaken to test whether the transmission advantage of infections that are virulent to vertebrates could be offset by an increased probability of causing death to their vectors. Mice were infected with one of seven distinct genetic clones of P. chabaudi that are known to vary in virulence. Infection virulence in mice (weight loss and anaemia) was positively correlated with mosquito infection rate but not with mosquito survival. Vector survival was influenced only by parasite clone and oocyst burden (negative association). These results suggest that vector fitness should not place an upper limit on malaria virulence. Overall, this research demonstrates that Plasmodium can be virulent to its vector, and that the magnitude of virulence is dependent on parasite genotype, infection diversity and environmental conditions. Although P. chabaudi virulence in vectors was not correlated with virulence in vertebrates, parasite genetic differences do impact vector fitness. Thus differential vector mortality could play an important role in determining the genetic composition of Plasmodium populations.
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Barclay, Victoria Charlotte. "Studies evaluating the possible evolution of malaria parasites in response to blood-stage vaccination." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3996.
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Drug resistance is one of the most medically relevant forms of pathogen evolution. To date, vaccines have not failed with the same depressing regularity as drugs. Does that then make vaccines evolution-proof? In the face of vaccination, pathogens are thought to evolve in two ways: by evolving epitope changes at the antigenic target of vaccination (epitope evolution); or by evolving changes at other antigenic loci, some of which may involve virulence (virulence evolution). The fundamental difference between these two forms of evolution is that virulence evolution could lead to disease outcomes in unvaccinated people that are more severe than would have been seen prior to evolution. One of the theoretical assumptions of virulence evolution is that more virulent parasites will have a selective advantage over less virulent parasites in an immunized host, and are thus more likely to be transmitted. The assumption is that more virulent parasites may be competitively more superior in mixed infections, or may be better able to evade/modulate the host immune response. Thus, the aim of this thesis was to experimentally test whether more virulent parasites have a within-host selective advantage in an immunized host or whether vaccine efficacy is more likely to depend on genetic differences at the targeted sites of vaccination. I used clones (genotypes) of the rodent malaria Plasmodium chabaudi originally derived from wild-caught Thicket (Thamnomys rutilans) rats to infect laboratory mice and a rodent analogue of the candidate blood-stage malaria vaccine apical membrane antigen 1 (AMA-1). I found that within-host selection did not depend on parasite virulence, and that protective efficacy depended on genotype-specific differences at the vaccine target. Vaccine-induced protection was not enhanced by including a number of allelic variants. However, such genotype-specific responses were only observed when the vaccine was tested against genetically distinct P. chabaudi parasites. When one P. chabaudi genotype was serially passaged through naïve mice the derived line was more virulent and was subsequently less well controlled by vaccine-induced immunity. In other experiments I found within host competition not to be immune-mediated. Thus my results suggest that vaccination has the potential to select for more virulent parasites but that the selective advantage is likely to be independent of competition. The selective advantage may be attributable to the enhanced immune evasion of more virulent parasites. However, without genetic markers of virulence, the mechanisms that mediate this selection remain unknown. My thesis contributes towards a growing body of evidence that vaccines have the potential to differently alter the within-host parasite dynamics of particular pathogen genotypes and that the selection imposed is likely to be system specific, depending on the fine specificity of the vaccine-induced responses and the identity of infecting parasites. Although vaccine potency may not be enhanced by including more than one allelic variant of an antigen, multi-valent vaccines may be one of the best ways to avoid the inadvertent selection for more virulent malaria parasites.
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Vardo-Zalik, Anne. "Clonal Diversity of the Malaria Parasite Plasmodium Mexicanum: Diversity Over Time and Space, and Effects on the Parasite’s Transmission, Infection Dynamics and Virulence." ScholarWorks @ UVM, 2008. http://scholarworks.uvm.edu/graddis/234.
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The biology of malaria parasites, Plasmodium spp., may be influenced by the presence of genetically distinct conspecific clones within a single infection, resulting in competition for host resources and transmission, and increased virulence for the vertebrate host. The extent of within host diversity, however, may be limited because overall clonal diversity could be reduced by the transmission biology of Plasmodium and variation in local prevalence. I examined clonal diversity of a natural malaria parasitehost association, P. mexicanum in its hosts, the western fence lizard, Sceloporus occidentalis, and sandflies, Lutzomyia vexator and L. stewarti, at a site in California ("Hopland"). Using microsatellite markers I characterized for the parasite, I examined (i) diversity within and among infections over time and space, (ii) transmission success of clones into both vector and lizard, (iii) the effects of clonal diversity on the parasite's infection dynamics and virulence for the lizard. From 1996 to 2006, clonal diversity varied both temporally and spatially, with slightly more multiclonal infections detected during years of high vs. low parasite prevalence (88% vs. 78% for sites with the highest prevalence at Hopland). Spatially, low prevalence sites (< 1% of lizards infected) had fewer multiclone infections (50%). Thus, even when prevalence drops over time, or at sites with chronically low prevalence, clonal diversity of the parasite remains high. Using natural and induced infections in the lizard, I found that multiclonal infections are no more infectious to vectors than single-clone infections, and almost all clones transfer successfully when the insect takes a blood meal. A competition experiment demonstrated that infections block new genotypes from entering a lizard host. Thus, multiclone infections are likely to be established when vectors feed on a complex infection and transmit those parasite clones to an uninfected lizard. The transmission biology of Plasmodium thus allows for the maintenance of genetic diversity in the parasite population. Finally, I examined the effects of multiclonality on the parasite's infection dynamics and virulence to the lizard host. Induced infections harboring a single or multiple clones had similar overall growth rates and maximal parasitemia, but multiclonal infections had significantly higher investment in gametocytes, suggesting competition for transmission. In addition, variation in parasite growth and density was greater for multiclonal infections, with approximately 1/3 displaying high replication rates and final parasitemia. Virulence measures indicated that weight change and proportion of immature erythrocytes was consistent for infections with 1, 2, 3 or > 3 clones, but the highly diverse infections had greater blood hemoglobin and glucose and more rapid clotting rates. Compared with the noninfected control lizards, highly diverse infections (3+) had higher blood glucose levels but similar hemoglobin levels. I have found that genetic diversity of the malaria parasite Plasmodium mexicanum varies both temporally and spatially, although overall diversity remains high. The transmission dynamics of the parasite maintains high genetic diversity within infections. Additionally, diversity within hosts plays a significant role in variation of infection dynamics and virulence.
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Cellier-Holzem, Elise. "Ecologie évolutive de la malaria aviaire : approches expérimentales des relations entre Plasmodium relictum et le canari domestique." Phd thesis, Université de Bourgogne, 2010. http://tel.archives-ouvertes.fr/tel-00665065.
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L'étude des interactions hôtes/parasites est actuellement un thème de recherche incontournable des sciences de l'évolution. Une des questions majeures soulevée par ces études est de comprendre pourquoi certains parasites provoquent des maladies mortelles, alors que d'autres restent relativement bénins pour leurs hôtes. Dans ce défi que tentent de relever les biologistes de l'évolution mais également les sciences médicales, nous avons choisi de nous intéresser à la malaria aviaire, et plus précisément à son représentant le plus commun dans les populations naturelles d'oiseaux : Plasmodium relictum. En procédant à des infections expérimentales de canaris domestiques (Serinus canaria), nous avons voulu comprendre quels facteurs liés aux caractéristiques du parasite et de l'oiseau (au niveau de l'individu ou de la population) pouvaient influencer la virulence de Plasmodium relictum. Nous avons ainsi pu mettre en évidence que des facteurs, tels que le passé infectieux de l'hôte, la dose de parasites reçue, la prévalence de ces derniers dans la population d'oiseaux ou bien encore les interactions sociales entre individus, pouvaient moduler les coûts d'une telle infection. La virulence est un trait composite qui dépend, certes, de l'exploitation de l'hôte par les parasites mais également de la réponse immunitaire de ce dernier contre l'infection. Nous avons pu le vérifier dans notre système expérimental en utilisant une approche immuno-écologique. Nous nous sommes enfin intéressée aux conditions favorisant l'évolution de la virulence : ce qui est essentiel pour comprendre l'émergence ou la réémergence de maladies infectieuses et pour développer des stratégies de contrôle de ces maladies.
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Diffendall, Gretchen. "Deciphering the role of an RNA Pol III-transcribed non-coding RNA in Plasmodium falciparum." Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS443.pdf.
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Le parasite protozoaire Plasmodium falciparum est l'agent causal de la forme la plus mortelle de paludisme humain. Ce pathogène utilise l'expression monoallélique de molécules d'adhésion de surface variantes, codées par la famille de gènes var, pour échapper au système immunitaire de l'hôte et provoquer une pathogenèse. On ne sait toujours pas comment l'activation du gène var fonctionne au niveau moléculaire et si des facteurs environnementaux peuvent moduler l'expression du gène var. Notre laboratoire a montré qu'une famille de gènes d'ARN non codants transcrits par Pol III, appelée RUF6, agit comme un trans-activateur des gènes var. Une association physique entre l'ARNnc RUF6 transcrit et le locus du gène var actif a été observée par FISH. La répression transcriptionnelle de tous les RUF6 par une stratégie d'interférence CRISPR spécifique a entraîné une régulation négative de la transcription de toute la famille des gènes var, suggérant une fonction potentielle de type amplificateur pour l'expression des gènes var. Une compréhension de la façon dont l'ARNnc RUF6 médie l'activation du gène var fait défaut. Ici, nous avons développé un protocole robuste de découverte protéomique dirigée par l'ARN (ChIRP-MS) pour identifier les interactions in vivo des protéines ARNnc RUF6. Des oligonucléotides antisens biotinylés ont été utilisés pour purifier l'interactome d'ARNnc RUF6. La spectrométrie de masse a identifié plusieurs protéines enrichies de manière unique qui sont liées à la transcription génique, telles que les sous-unités d'ARN Pol II, les protéines d'assemblage des nucléosomes et un homologue de la Dead-Box Helicase 5 (DDX5). La purification par affinité de PfDDX5 a identifié plusieurs protéines trouvées à l'origine par notre protocole RUF6-ChIRP, validant la robustesse de la technique pour l'identification des interactomes d'ARNnc chez P. falciparum. Le déplacement inductible de PfDDX5 nucléaire a entraîné une importante régulation à la baisse du gène var actif. Notre travail identifie un complexe protéique RUF6 ARNnc qui interagit avec l'ARN Pol II pour soutenir l'expression du gène var. Nous postulons que l'hélicase DDX5 peut résoudre les structures secondaires G-quadruplex hautement enrichies en gènes var pour faciliter l'activation et la progression de la transcription. De plus, nous découvrons des facteurs environnementaux qui déclenchent une régulation négative de la transcription du gène var. Nous observons que la privation d'isoleucine et les concentrations élevées de MgCl2 dans le milieu inhibent les gènes transcrits par l'ARN polymérase III. Il est important de noter que cela inclut une famille de gènes ARNnc régulateurs spécifiques de P. falciparum (codée par la famille de gènes RUF6) qui est un régulateur clé de l'activation du gène var. Nous avons identifié un gène homologue à l'eucaryote Maf1 hautement conservé, en tant qu'effecteur négatif de la transcription de l'ARNnc RUF6. Des concentrations élevées de MgCl2 ont entraîné un déplacement de PfMaf1 cytoplasmique vers le compartiment nucléaire. Nous avons utilisé un système de dégradation inductible des protéines pour montrer que les stimuli externes dépendent de PfMaf1 pour déclencher une expression plus faible des gènes RUF6. Nos résultats indiquent une voie indépendante de TOR qui répond aux changements de l'environnement et réprime la transcription Pol III. Ce travail fournit des informations conceptuelles nouvelles et importantes sur la répression de la virulence du parasite dépendante de PfMaf1 qui peuvent être très pertinentes pour établir la persistance subclinique du parasite pendant la saison sèche. Pris ensemble, ces résultats aident à mieux comprendre la fonction et la régulation d'un ARNnc impliqué dans la régulation de la variation antigénique et de la pathogenèse chez P. falciparum. Notre validation de la technique ChIRP-MS permet de futures études dans l'identification des protéines de liaison à l'ARN pour les ARNnc dont la fonction [...]The protozoan parasite Plasmodium falciparum is the causative agent of the deadliest form of human malaria. This pathogen uses monoallelic expression of variant surface adhesion molecules, encoded by the var gene family, to evade the host immune system and cause pathogenesis. It remains unclear how monoallelic expression of var gene activation works at the molecular level and if environmental factors can modulate var gene expression. Our laboratory showed a Pol III transcribed GC-rich non-coding RNA gene family, termed RUF6, acts as a trans-activator of var genes. A physical association between the transcribed RUF6 ncRNA and the active var gene locus was observed through FISH. Transcriptional repression of all RUF6 by a specific CRISPR interference strategy resulted in transcriptional down regulation of the entire var gene family, suggesting a potential enhancer-like function to var gene expression. An understanding of how RUF6 ncRNA mediates var gene activation is lacking. Here we developed a robust RNA-directed proteomic discovery (ChIRP-MS) protocol to identify in vivo RUF6 ncRNA protein interactions. Biotinylated antisense oligonucleotides were used to purify the RUF6 ncRNA interactome. Mass spectrometry identified several uniquely enriched proteins that are linked to gene transcription such as RNA Pol II subunits, nucleosome assembly proteins, and a homologue of the Dead-Box Helicase 5 (DDX5). Affinity purification of PfDDX5 identified several proteins originally found by our RUF6-ChIRP protocol, validating the robustness of the technique for the identification of ncRNA interactomes in P. falciparum. Inducible displacement of nuclear Pf-DDX5 resulted in the significant down-regulation of the active var gene. Our work identifies a RUF6 ncRNA protein complex that interacts with RNA Pol II to sustain var gene expression. We postulate that DDX5 helicase may resolve G-quadruplex secondary structures highly enriched in var genes to facilitate transcriptional activation and progression. Furthermore, we discovered environmental factors that trigger downregulation of var gene transcription. We observe that isoleucine starvation and high MgCl2 concentrations in the medium inhibit RNA Polymerase III transcribed genes. Importantly, this includes a P. falciparum-specific regulatory ncRNA gene family (encoded by the RUF6 gene family) that is a key regulator in var gene activation. We identified a homologous gene to the highly conserved eukaryotic Maf1, as a negative effector of RUF6 ncRNA transcription. Elevated MgCl2 concentrations led to a shift of cytoplasmic PfMaf1 to the nuclear compartment. We used an inducible protein degradation system to show that external stimuli depend on PfMaf1 to trigger lower expression of RUF6 genes. Our results point to a TOR independent pathway that responds to changes in the environment and represses Pol III transcription. This work provides new and important conceptual insights into PfMaf1-dependent repression of parasite virulence that may be highly relevant for establishing subclinical parasite persistence in the dry season. Taken together, these results help to better understand the function and regulation of a ncRNA involved in regulating the antigenic variation and pathogenesis in P. falciparum. Our validation of the ChIRP-MS technique allows for future studies in identifying RNA-binding proteins for ncRNAs whose function remains to be fully characterized
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Neal, Aaron T. "Identifying genetic determinants of impaired PfEMP1 export in Plasmodium falciparum-infected erythrocytes." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:0cc3f09c-9178-448b-92f8-8f9564398585.
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The virulence of Plasmodium falciparum is largely attributed to the ability of asexual blood-stage parasites to cytoadhere to the microvascular endothelium of the human host. This pathogenic behavior is mediated by the primary parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), an understanding of which is crucial to develop interventions to ameliorate the morbidity and mortality of P. falciparum malaria. The work presented in this thesis describes the application of a phenotype-to-genotype experimental approach to identify novel parasite proteins involved in the trafficking and display of PfEMP1. Guided by the overall hypothesis that the in vitro culture-adapted parasite line 3D7 harbors 1 or more genetic determinants of impaired PfEMP1 trafficking, surface PfEMP1 levels were first measured in 3D7, the presumably trafficking-competent parasite line HB3, and 16 unique progeny from an HB3 x 3D7 genetic cross (chapter 2). These phenotypes were then combined with genome-wide SNP data in QTL analysis to identify genetic polymorphisms potentially responsible for the impaired trafficking in 3D7 (chapter 3). A near-significant QTL containing a single protein-coding gene, the putative kinesin Pf3D7_1245600, was identified, characterized, and investigated in CRISPR-Cas9-driven allele-exchange parasite transfection experiments to establish a causal link between the gene and PfEMP1 trafficking (chapter 4). The parasite transfections were unsuccessful, but the potential role of Pf3D7_1245600 in PfEMP1 trafficking was indirectly assessed through the disruption of microtubules with colchicine (chapter 4), which significantly impacted the surface PfEMP1 levels of HB3 but not 3D7. The findings of this thesis suggest that kinesins and microtubules may play previously unconsidered roles in the regulation, production, or trafficking of PfEMP1.
Book chapters on the topic "Malaria virulence"
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Escalante, Ananias A., and Francisco J. Ayala. "Malaria: Host Range, Diversity, and Speciation." In Evolution of Virulence in Eukaryotic Microbes, 91–110. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch5.
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Su, Xin-Zhuan, and John C. Wootton. "Selective Sweeps in Human Malaria Parasites." In Evolution of Virulence in Eukaryotic Microbes, 124–42. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch7.
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Smith, Joseph, and Kirk W. Deitsch. "Antigenic Variation, Adherence, and Virulence in Malaria." In Evolution of Virulence in Eukaryotic Microbes, 338–61. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch18.
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Duraisingh, Manoj T., Jeffrey D. Dvorin, and Peter R. Preiser. "Invasion Ligand Diversity and Pathogenesis in Blood-Stage Malaria." In Evolution of Virulence in Eukaryotic Microbes, 362–83. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch19.
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Volkman, Sarah K., Daniel E. Neafsey, Stephen F. Schaffner, Pardis C. Sabeti, and Dyann F. Wirth. "From Population Genomics to Elucidated Traits inPlasmodium Falciparum: Population Genomics, Genetic Diversity, and Association in Malaria." In Evolution of Virulence in Eukaryotic Microbes, 111–23. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch6.
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Carter, Richard, and Richard Culleton. "Genetic Mapping of Virulence in Rodent Malarias." In Evolution of Virulence in Eukaryotic Microbes, 269–84. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118308165.ch14.
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Tsegaye Tseha, Sintayehu. "Plasmodium Species and Drug Resistance." In Plasmodium Species and Drug Resistance [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98344.
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Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.
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Gupta, Sunetra, and Karen Day. "Virulence and transmissibility in P. falciparum malaria." In Models for Infectious Human Diseases, 160–80. Cambridge University Press, 1996. http://dx.doi.org/10.1017/cbo9780511662935.018.
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Ewald, Paul W. "Vectors, Vertical Transmission, and the Evolution of Virulence." In Evolution of Infectious Disease, 35–56. Oxford University PressNew York, NY, 1994. http://dx.doi.org/10.1093/oso/9780195060584.003.0003.
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Abstract Why has falciparum malaria been so lethal and the common cold so mild? The first step toward an answer is to identify the trade offs associated with different levels of virulence. Consider first a parasite that depends on the mobility of the host for transmission. Rhinoviruses, for example, cause the common cold by reproducing inside the cells that line our nasal passages. The viruses are shed from these cells into nasal secretions, which trickle out through a runny nose or blast out in droplets during a sneeze. The trickle may be blocked with a finger, which then may contact fingers of others during a hand shake or by way of a borrowed pencil. When these contacted fingers then contact the noses to which they belong, or when these noses inhale the droplets from a sneeze, some lucky rhinoviruses may be planted onto fertile ground. Whichever of the two routes occurs, host mobility is critical.
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"Malaria Parasite Virulence in Mosquitoes and Its Implications for the Introduction and Efficacy of GMM Malaria Control Programmes." In Genetically Modified Mosquitoes for Malaria Control, 119–32. CRC Press, 2006. http://dx.doi.org/10.1201/9781498712866-13.
Full textConference papers on the topic "Malaria virulence"
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Miranda Mas, Carlos. "Arte vs turistificación: Souvenirs de resistencia." In V Congreso Internacional de Investigacion en Artes Visuales ANIAV 2022. RE/DES Conectar. València: Editorial Universitat Politècnica de València, 2022. http://dx.doi.org/10.4995/aniav2022.2022.15485.
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Esta comunicación plantea una investigación artística que atiende a uno de los efectos de la hiperconexión territorial global: los procesos de turistificación de que son objeto muchas ciudades, naturalizados como destino postcapitalista inalterable y que, aquí, propongo repensar mediante una serie de pinturas y esculturas. Así, éstas parten de la asimilación del consumo de recuerdos de viaje durante el primer fenómeno turístico (ss. XVIII y XIX), aquel Grand Tour que llevaba a potentados e intelectuales del norte de Europa hacia “exóticos” lugares del Sur y de Oriente. En el caso particular de Málaga, esos souvenirs se concretaban en los llamados “barros malagueños” (Malaga clay figures), pequeñas piezas de barro cocido y pintado que tuvieron entonces gran desarrollo comercial en la ciudad, las cuales representaban los tópicos culturales que la mirada orientalista de aquellos viajeros proyectaba sobre la Europa mediterránea. El desplazamiento que articulo toma aquella imaginería de bandoleros, manolas, bailaores, etc. para asociarla a la actual turistificación sistemática que sufren localidades históricas de todo el mundo, destacando el proceso malagueño por la rapidez y virulencia con la que este fenómeno de conversión en ciudades-marca como atractores de turismo masivo está modificando su estructura social, urbana, económica y política. Por tanto, estas obras articulan una relectura irónica de aquellos “barros malagueños” para, conservando intactas sus poses figurativas de marcado carácter goyesco, realizar una serie paralela de esculturas y pinturas que convierten los originarios tipos costumbristas en los actuales turistas “de fiesta y borrachera”, disfrutando de la culminación en clave perversa de aquella mirada romántica hoy devenida en devastadora ceguera consumista. El antiguo souvenir, pues, presta aquí su originaria iconología festiva y tópica a la reversión actualizada de su sentido: de recuerdo del viajero ilustrado pasa a ser arma representacional del indígena actual ante los desmanes de la actual turistificación.
Reports on the topic "Malaria virulence"
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McElwain, Terry F., Eugene Pipano, Guy H. Palmer, Varda Shkap, Stephn A. Hines, and Wendy C. Brown. Protection of Cattle against Babesiosis: Immunization against Babesia bovis with an Optimized RAP-1/Apical Complex Construct. United States Department of Agriculture, September 1999. http://dx.doi.org/10.32747/1999.7573063.bard.
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Previous research and current efforts at control of babesiosis fall short of meeting the needs of countries where the disease is endemic, such as Israel, as well as the needs of exporting countries and countries bordering on endemic areas, such as the U.S. Our long-term goal is to develop improved methods of immunization against bovine babesiosis based on an understanding of the molecular mechanisms of immune protection and parasite targets of a protective immune response. In our previous BARD project, we established the basis for focusing on rhoptry antigens as components of a subunit vaccine against bovine babesiosis, and for additional research to better characterize rhoptry associated protein-1 (RAP-1) as a target of protective immunity. In this continuation BARD project, our objectives were to [1] optimize the immune response against RAP-1, and [2] identify additional rhoptry candidate vaccine antigens. The entire locus encoding B. bovis RAP-1 was sequenced, and the rap-1 open reading frame compared among several strains. Unlike B. bigemina, in which multiple gene copies with variant domains encode RAP-1, the B. bovis RAP-1 locus contains only two identical genes which are conserved among strains. Through testing of multiple truncated constructs of rRAP-1, one or more immunodominant T cell epitopes were mapped to the amino terminal half of RAP-1. At least one linear and one conformational B cell epitope have been demonstrated in the same amino terminal construct, which in B. bigemina RAP-1 also contains an epitope recognized by neutralizing antibody. The amine terminal half of the molecule represents the most highly conserved part of the gene family and contains motifs conserved broadly among the apicomplexa. In contrast, the carboxy terminal half of B. bovis RAP-1 is less well conserved and contains multiple repeats encoding a linear B cell epitope potentially capable of inducing an ineffective, T cell independent, type 2 immune response. Therefore, we are testing an amino terminal fragment of RAP-1 (RAP-1N) in an immunization trial in cattle. Cattle have beer immunized with RAP-1N or control antigen, and IL-12 with Ribi adjuvant. Evaluation of the immune response is ongoing, and challenge with virulent B. bovis will occur in the near future. While no new rhoptry antigens were identified, our studies did identify and characterize a new spherical body antigen (SBP3), and several heat shock proteins (HSP's). The SBP3 and HSP21 antigens stimulate T cells from immune cattle and are considered new vaccine candidates worthy of further testing. Overall, we conclude that a single RAP-1 vaccine construct representing the conserved amino terminal region of the molecule should be sufficient for immunization against all strains of B. bovis. While results of the ongoing immunization trial will direct our next research steps, results at this time are consistent with our long term goal of designing a subunit vaccine which contains only the epitopes relevant to induction of protective immunity. Parallel studies are defining the mechanisms of protective immunity. Apicomplexan protozoa, including babesiosis and malaria, cause persistent diseases for which control is inadequate. The apical organelles are defining features of these complex protozoa, and have been conserved through the evolutionary process, Past and current BARD projects on babesiosis have established the validity and potential of exploiting these conserved organelles in developing improved control methods applicable to all apicomplexan diseases.
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Lignes directrices pour le contrôle et la prévention de la peste des petits ruminants (PPR) dans les populations de faune sauvage. OIE (World Organisation for Animal Health), December 2021. http://dx.doi.org/10.20506/ppr.3274.
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La peste des petits ruminants (PPR) est une maladie animale des petits ruminants domestiques et des artiodactyles sauvages, très répandue, virulente et dévastatrice, causée par le virus de la peste des petits ruminants, un morbillivirus. Le taux de mortalité peut dépasser 90 %, en particulier dans les populations naïves au plan immunologique, souffrant de malnutrition et soumises à des stress. Ces lignes directrices sont destinées à aider les pays à élaborer et à mettre en œuvre leur programme d’éradication de la PPR ; elles incluent des objectifs, des politiques et des stratégies qui sont adaptables à l’ensemble des besoins nationaux et qui favorisent l’intégration du secteur en charge de la faune sauvage dans le plan stratégique national.