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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apart from cellular immunity and immunopathology, various cytokines have been implicated in malaria-associated immunosuppression. In this study, serum levels of transforming growth factor-beta (TGF-beta) were determined with an enzyme-linked immunosorbent assay in 37 patients with acute Plasmodium falciparum malaria prior to, during, and after therapy and in 17 healthy controls in Bangkok, Thailand. Patients were treated with artesunate and mefloquine. TGF-beta serum levels were found decreased prior to treatment (14 +/- 11 pg/ml versus 63 +/- 15 pg/ml in healthy controls; P < 0.05). The serum concentrations of TGF-beta increased after initiation of treatment and were within normal range on day 21. Serum levels of both tumor necrosis factor-alpha (TNF-alpha) and soluble TNF-receptor 55 kDa were inversely correlated to serum levels of TGF-beta (r = -0.667 and r = -0.592, n = 37; respectively, P < 0.05 for both). No correlation between parasitemia and serum levels of TGF-beta could be found. The results are compatible with a decreased production and release, an enhanced clearance or utilization, or tissue accumulation of TGF-beta in acute P. falciparum malaria.
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PMID:Decreased serum levels of TGF-beta in patients with acute Plasmodium falciparum malaria. 755 10

Plasmodium cynomolgi B has been used to infect the rhesus monkey to study the histochemical changes (lipid infiltration, glycogen, protein, DNA and RNA) in liver, kidney and spleen during early (exoerythrocytic) and late (chronic) stages of malarial infection. Infected liver showed significant lipid infiltration during exoerythrocytic and erythrocytic (acute phase) stage of infection. Kidney showed lipid deposition during acute phase of infection while spleen sections were negative for lipid depositions. As a result of malarial infection there was significant depletion of glycogen in liver during exoerythrocytic stage of infection. Glycogen content increased in liver and kidney during erythrocytic stage of infection. The spleen which is the main target of immunopathology in malaria showed no change in glycogen content. During exoerythrocytic phase host tissue organs showed no change in protein and nucleic acids while erythrocytic phase showed slightly increased proteins in liver and kidney. Nucleic acids became decreased in liver and spleen during erythrocytic phase of infection. The parasite used in this study has a defined prepatent period, can be cyclically passaged with ease and non fatal in nature.
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PMID:Histochemical changes in host tissues from Plasmodium cynomolgi B infected rhesus monkey (Macaca mulatta). 864 16

Recently it has become evident that he same candidate antigen can be shared by several of the parasite stages, and thus the concept of a multistage vaccine is becoming more and more attractive. A TDR Task Force evaluated the promise and stage of development of some 20 existing asexual blood stage candidate antigens and prepared a strategy for their development leading to clinical testing and field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen (EBA). A field study conducted in Tanzanian children showed that the SPf66 Colombian vaccine was safe, induced antibodies, and reduced the risk of developing clinical malaria by around 30%. This study, confirmed the potential of the vaccine to confer partial protection in areas of high as well as low intensity of transmission. Pfs25 is a leading candidate antigen for a transmission blocking vaccine. It is found in the ookinete stage of the parasite in the mosquito midgut. Gramme amounts of GMP-grade material have been produced and a vaccine based on the Pfs25 antigen formulated with alum should have gone into phase I and II clinical trials in the USA and Africa during 1995. Because the first malaria prototype vaccine to be tried out in people on a large scale has been the polymerized synthetic peptide developed by patarroye on the basis of the SPf66 antigen of P. faliciparum, the results are with much interest. It is still premature to predict the effectiveness of this vaccine globally, but its development will encourage further progress in a fields that has repeatedly been characterized by raised and then dashed drops. These various vaccines are based on the classical approach to vaccination, which is to raise host immunity against the parasite so as to reduce parasite densities or to sterilize an infection. A newer approach is development of antidisease vaccines which aim to alleviate morbidity by suppressing immunopathology in the host. Antidisease vaccines are based on neutralizing parasite components that induce host pathology, leaving the parasite itself directly unaffected. These effects would occur when each type of the disease is considered by it self; however, synergistic effects may be expected when they are used in combination. The rational for vaccines based on any of these stages was that immunization of various hosts with whole parasites of each of these stages has been able to induce protection or total transmission-blocking immunity. Less significant but not to be discounted is the fact that natural malaria infections in humans have been shown to induce immunity against every one of these parasite stages against which vaccines are being developed, an exception to this are those stages that are present only in the mosquito vector with component molecules not presented to the human host, such as exclusively ookinete antigens. For several very apparent reasons a vaccine today is conceived of as subnit as opposed to show1 parasite vaccines, either in the form of a recombinant product or as synthetic peptide constructs. Genes coding for several antigens of P. falciparum and some of P. vivax have been seems to be common to many Plasmodium antigens; this is that they contain tandem repeats of oligopeptide sequences which often code for immunodominant epitopes. Following several decades of research on malaria vaccine development, the field at a glace may present a conflicting picture, with several achievements, and some disappointments and controversies. Issues facing the development of a malaria vaccine are complex. It is not clear how far we may yet be from achieving this goal. The work of the past decades has laid an extensive foundation of ralevant knowledge and technologies, and the goal it self remains as important as ever, will scientists remain committed to this objective?
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PMID:Malaria vaccine. 900 71

Vgamma9Vdelta2-encoded T cell receptors (TCR) expressed by most human peripheral blood gammadelta T cells mediate the recognition of nonpeptidic phosphoantigens from various pathogens without any known requirement for HLA molecules. Functionally mature Vgamma9Vdelta2 T cells display a potent natural killer (NK)-like cytotoxic activity, share with NK cells the expression of inhibitory receptors for HLA class I molecules, and release a plethora of cytokines, most notably interferon-gamma and tumor necrosis factor alpha. Hence, through local activation, the early recruitment and stimulation of Vgamma9Vdelta2 T cells may promote efficient anti-infectious immunity. However, a chronic overactivation of this T cell subset may result in immunopathology. The meeting held in St. Vincent, Val d'Aosta, Italy (symposium on gammadelta T cells in natural immunity to infections: a rationale for vaccine development organized by the World Foundation for AIDS Research and Prevention, the UNESCO, and the Italian National Research Council, December 2-4, 1996) focused on the importance of gammadelta T cell activation and anergy for the pathogenesis of tuberculosis, malaria, and HIV infections.
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PMID:Gammadelta T cell activation or anergy during infections: the role of nonpeptidic TCR ligands and HLA class I molecules. 930 66

Malaria continues to extract an incalculable cost on human morbidity and mortality throughout tropical and subtropical regions of the world, and effective control measures are urgently needed. Despite considerable efforts in recent years to develop subunit vaccines targeted at various stages of the Plasmodium life-cycle, the commercial availability of a vaccine is still a distant prospect. One of the underlying difficulties hindering successful vaccine design is our incomplete knowledge of the precise type(s) of immune response to aim for, and then how to achieve it. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues on how manipulation of the immune system may best be achieved. Ten years have passed since the identification of the Th1/Th2 paradigm for distinguishing CD4+ T cells according to cytokine secretion patterns which determine their function. This review summarises our progress towards understanding the broad spectrum of immune responsiveness to the blood stages of the malaria parasite during experimental infections in mice and highlights the way in which examination of rodent malarias provides a powerful tool to dissect the interaction of Th1 and Th2 cells during an immune response to an infectious disease agent. It is proposed that the pliability of rodent systems for investigating immunoregulation provides valuable insight into the balance between protection and pathology in human malaria and throws light on the factors involved in the modulation of vaccine-potentiated immunity.
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PMID:Immunoregulation of malarial infection: balancing the vices and virtues. 950 41

Malaria is the world's major parasitic disease, for which effective control measures are urgently needed. One of the difficulties hindering successful vaccine design against Plasmodium is an incomplete knowledge of antigens eliciting protective immunity, the precise types of immune response for which to aim, and how these can be induced. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues to how manipulation of the immune system may best be achieved. We are studying the regulation of the balance between T helper 1 (Th1) and T helper 2 (Th2) CD4+ T lymphocytes in immunity to asexual blood stages of malaria responsible for the pathogenicity of the disease. Protective immunity to the experimental murine malarias Plasmodium chabaudi and Plasmodium yoelii involves both Th1 and Th2 cells, which provide protection by different mechanisms at different times of infection characterised by higher and lower parasite densities, respectively. This model therefore facilitates a clearer understanding of the Th1/Th2 equilibrium that appears central to immunoregulation of all host/pathogen relationships. It also permits a detailed dissection in vivo of the mechanisms of antimalarial immunity. Here, we discuss the present state of malaria vaccine development and our current research to understand the factors involved in the modulation of vaccine-potentiated immunity.
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PMID:A role for cytokines in potentiation of malaria vaccines through immunological modulation of blood stage infection. 1058 67

Malaria is the world's major parasitic disease, for which effective control measures are urgently needed. One of the difficulties hindering successful vaccine design against Plasmodium is an incomplete knowledge of antigens eliciting protective immunity, the precise types of immune response for which to aim, and how these can be induced. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues to how manipulation of the immune system may best be achieved. This review discusses the current state of malaria vaccine development and research to understand the factors involved in the modulation of vaccine-potentiated immunity to the pathogenic blood-borne stages of the parasite.
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PMID:Vaccination against malaria: targets, strategies and potentiation of immunity to blood stage parasites. 1070 81

A common feature of autoimmunity is the presence of autoantibodies (AAb). Two types of AAb have been described: the 'pathogenic' AAb, associated with autoimmune diseases (AID), and the so-called 'natural' AAb. The latter are present in all normal individuals and have been postulated to play a major role as a first defensive barrier of the organism. Both the 'pathogenic' and the 'natural' AAb can be detected at higher frequencies among individuals exposed to viral, bacterial and parasitic infections. The malaria associated AAb do not seem to result from a generalised polyclonal B-cell activation (PBA), have specificities that may differ according to the degree of clinical immunity and do not seem to be pathogenic. Malaria may offer a protective effect against AID, by diminishing its severity or by either preventing or retarding its expression. AAb could also participate in the immune protection against malaria, and this could happen in several ways: (i) AAb directed to modified Ag expressed on the red blood cell (RBC) membrane during parasitisation and (ii) AAb reactive with crypto- or neo-Ag revealed on both normal and infected RBC membranes, by destroying infected, and also normal, erythrocytes; (iii) anti-idiotype AAb specific of the binding site of anti-merozoite Ab, which would mimic the parasite ligand for the RBC receptor, by competing with parasites and blocking RBC invasion; (iv) AAb cross-reactive with parasite material - such as nuclear or cytoskeleton Ag - having a direct parasiticide activity; (v) the natural AAb network, through its 'anti-bacterial first defense barrier'; and finally (vi) anti-phospholipid (PL) AAb, by neutralizing the pathogenic properties of parasite-derived PL. Finally, in view of currently available knowledge, it is concluded that, since AAb are not always pathogenic, the price for an 'autoimmunity-mediated' protection in malaria would not necessarily be immunopathology and clinical autoimmunity, and a protective role of AAb could be exerted with no danger to the host.
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PMID:Autoimmunity and malaria: what are they doing together? 1097 61

Glycosylphosphatidylinositols (GPIs), the anchor molecules of some membrane proteins of Plasmodium species, have been implicated in the induction of immunopathology during malaria infections. Hence, neutralization of GPIs by antibodies may reduce the severity of clinical attacks of malaria. To test this hypothesis, we have assessed the levels of anti-GPI antibodies in plasma from children and adults living in areas of seasonal malaria transmission in The Gambia. In a prospective study of susceptibility to clinical or asymptomatic infection, the levels of anti-GPI antibodies were measured before and after the transmission season. Samples were also obtained from children recruited into a hospital-based study of severe malaria. We find that in malaria-exposed individuals both the prevalence and the concentration of anti-GPI antibodies increase with age and that antibody levels are significantly higher at the end of the malaria transmission season than at the start of the season. Antibody levels are also higher in children with asymptomatic infections (i.e., those with a degree of clinical immunity) than in children who developed clinical malaria and high parasitemia, although this difference is not statistically significant. Importantly, antibodies appear to be rapidly boosted by clinical malaria infection, but children under the age of two years are seronegative for anti-GPI antibodies, even during an acute infection. While GPIs may be involved in the pathogenesis of human malaria, the data from this study do not provide any strong evidence to support the notion that anti-GPI antibodies confer resistance to mild or severe malarial disease. Further case-control studies, ideally of a prospective nature, are required to elucidate the role of antiglycolipid antibodies in protection from severe malaria.
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PMID:Prevalence and boosting of antibodies to Plasmodium falciparum glycosylphosphatidylinositols and evaluation of their association with protection from mild and severe clinical malaria. 1218 51

Throughout history malaria has proved to be a significant threat to human health. Between 300 and 500 million clinical cases occur each year worldwide, approximately 2 million of which are fatal, primarily in children. The vast majority of malaria-related deaths are due to infection with Plasmodium falciparum; P. vivax causes severe febrile illness but is rarely fatal. Following repeated exposure to infection, people living in malaria endemic areas gradually acquire mechanisms to limit the inflammatory response to the parasite that causes the acute febrile symptoms (clinical immunity) as well as mechanisms to kill parasites or inhibit parasite replication (antiparasite immunity). Children, who have yet to develop protective immune mechanisms are thus at greater risk of clinical malaria, severe disease and death than adults. However, two epidemiological observations indicate that this is, perhaps, an oversimplified model. Firstly, cerebral malaria - a common manifestation of severe malaria - typically occurs in children who have already acquired a significant degree of antimalarial immunity, as evidenced by lower mean parasite densities and resistance to severe anaemia. One potential explanation is that cerebral malaria is, in part, an immune-mediated disease in which immunological priming occurs during first infection, eventually leading to immunopathology on re-infection. Secondly, among travelers from nonendemic areas, severe malaria is more common - and death rates are higher - in adults than in children. If severe malaria is an immune-mediated disease, what might be priming the immune system of adults from nonendemic areas to cause immunopathology during their first malaria infection, and how do adults from endemic areas avoid severe immunopathology? In this review we consider the role of innate and adaptive immune responses in terms of (i) protection from clinical malaria (ii) their potential role in immunopathology and (iii) the subsequent development of clinical immunity. We conclude by proposing a model of antimalarial immunity which integrates both the immunological and epidemiological data collected to date.
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PMID:The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. 1286 17


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