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

Histopathologic and immunohistologic studies were performed in two cases of fatal cerebral malaria. On admission, both patients were in unarousable coma with hyperparasitemia. Examination of the tissue sections from various organs showed parasite sequestration in both cases with more extensive area of sequestration in case 1 than in case 2. A panel of monoclonal antibodies against cytokines applied to these tissues clearly detected tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), interleukin-1beta (IL-1beta), and IL-10 in the tissues from brain and liver of case 1. A different cytokine profile, IL-4 and IL-10, was found in the brain tissues of case 2; no TNF alpha nor IFN gamma was detected. There was no cytokine detected in the tissues of other organs in either case. Results of the study suggest that histopathology in the brain of fatal cerebral malaria may be associated with focal accumulation of cytokines. Additionally, the type of cytokines produced locally in a particular tissue during malaria infection may be regulated by the degree of regional parasite sequestration.
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PMID:Involvement of cytokines in the histopathology of cerebral malaria. 939 86

A single Plasmodium falciparum isolate was adapted for growth in serum-free culture medium. The parasitemia increased from 0.5% to 20% on day 7 after thawing. The asexual forms of the parasites appeared morphologically normal and pigment formation was comparable with that seen under standard conditions with serum present. Parasites were coincubated in 96-well plates with serum, peripheral blood mononuclear cells (PBMC), and PBMC in the presence of autologous serum from healthy non-immune individuals (n = 12), healthy semi-immune individuals (n = 12), and malaria patients (n = 7). Growth was monitored for six days. The concentration of interleukin-6 and interferon-gamma (IFN-gamma) in supernatants from the continuous cultures were measured by a bioassay and an enzyme-amplified sensitivity immunoassay. The results of this study showed that parasites cultured in serum-free medium in the presence of PBMC develop more rapidly, particularly with cells from malaria patients, compared with parasites cultured alone. The growth of parasites was different if 10% autologous serum was added to the culture. Parasite growth with sera from acutely infected individuals was similar with that with sera from aparasitemic, nonimmune individuals, and both supported significantly higher parasite growth over the six-day culture period compared with sera from the uninfected semi-immune individuals. Production of IFN-gamma by cells from nonimmune individuals and malaria patients was higher when cultures did not contain autologous serum. Nonimmune donor cells produced high amounts of IFN-gamma, but cells from the semi-immune donors produced little of this cytokine. There was no marked inhibition of parasite growth with any combination of serum and cells over six days of culture. A difference between the groups was observed after two days of culture, when growth with cells and serum from the uninfected, semi-immune group was significantly lower than that from the nonimmune group, but this was not subsequently sustained. The results of the study show that continuous cultivation of P. falciparum in serum-free medium provides a novel in vitro model to study mechanisms of the interplay between components of the human immune system and the malarial parasite, in which any possible influence of human serum is removed.
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PMID:Differential effects of human serum and cells on the growth of Plasmodium falciparum adapted to serum-free in vitro culture conditions. 939 1

In this review we summarise the arguments that inflammatory cytokines, triggered by material released from the parasite at schizogony (malarial toxin), might induce the illness and pathology seen in malaria. These pro-inflammatory cytokines can generate inducible nitric oxide synthase and cause nitric oxide to be released, as can low concentrations of malarial toxin itself provided interferon-gamma, which has only low activity in the absence of malarial toxin, is present. We suggest here that recently described hypermetabolic functions of these mediators provide a much more plausible explanation for malarial hyperlactataemia and hypoglycaemia, the chief prognostic indicators in falciparum malaria, than does hypoxia secondary to mechanical blockage of vessels by sequestering parasites, which is the dominant current theory. We also review the arguments that rationalise, through these mediators, the reversibility of the coma of cerebral malaria. Although not yet tested at a cellular level, the proposal that nitric oxide generated in cerebral vascular walls contributes to this coma continues to gather indirect support. In addition, new evidence incriminating nitric oxide in the mechanism of tolerance to endotoxin rationalises the raised nitric oxide generation seen in malarial tolerance.
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PMID:The biological basis of malarial disease. 939 94

Tumour Necrosis Factor (TNF) is produced at the initiation of malaria infections (pre-erythrocytic phase), as demonstrated by the release of bioactive TNF by peripheral blood mononuclear cells from individuals residing in endemic areas after stimulation with stage specific sporozoite antigens. During the erythrocytic phase, TNF production is greatly augmented by parasite antigens at the time of schizont rupture and merozoite release from infected erythrocytes. Some of the strongest inducers of TNF synthesis and release are malaria toxins, e.g. glycosylphosphatidylinositol moieties and malaria pigment. Because of TNF's well-known cytotoxic activity it was originally hypothesized that it alone was responsible for killing parasites directly or within host cells. Though earlier reports of the capability of serum containing TNF to kill plasmodia supported this idea, later experiments with recombinant TNF showed a lack of significant parasiticidal activity. Recent studies investigating related factors showed that they were involved with TNF in the control of infection. These factors included -ther cytokines, such as interleukin (IL)-1, IL-6, IL-12, interferon-gamma (IFN gamma) as well as nitric oxide intermediates (NOI) and reactive oxygen intermediates (ROI). This positioned TNF as a key regulator of the immune response against the malaria parasite. However, it must be noted that TNF and its associated factors are also responsible for the fever, aches and pains of acute illness, as well as the hypoglycemia, shock, bleeding and reversible coma of severe malaria seen in approximately 1 percent of individuals with malaria. Therein lies the rub; factors important in the control of malaria also appear to have detrimental properties. Research presented in this review characterizes TNF and associated cytokines' importance in the immune response to malaria.
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PMID:Tumour necrosis factor and associated cytokines in the host's response to malaria. 939 95

Merozoite surface protein 2 (MSP2) is a malaria vaccine candidate currently undergoing clinical trials. We analyzed the peripheral blood mononuclear cell (PBMC) response to synthetic peptides corresponding to conserved and variant regions of the FCQ-27 allelic form of MSP2 in Ghanaian individuals from an area of hyperendemic malaria transmission and in Danes without exposure to malaria. PBMC from 20-39% of Ghanaians responded to each of the peptides by proliferation and 29-36% had PBMC which produced interferon-gamma (IFN-gamma) in response to peptide stimulation. In Danes, there was no proliferation to two of the peptides and only PBMC from 5% of the individuals proliferated to the other three peptides. IFN-gamma production was not detected to any peptide. In both Danes and Ghanaians in only a few instances was IL-4 detected in the PBMC cultures. Overall PBMC from 79% of the Ghanaians responded by proliferation and/or cytokine secretion to at least one of three peptides tested, whereas responses were only observed in 14% of Danes (P = 0.002). These data suggest that the Ghanaians had expanded peripheral blood T-cell populations recognizing the peptides as a result of natural infection. The findings are encouraging for the development of a vaccine based on these T-epitope containing regions of MSP2, as the peptides were broadly recognized suggesting that they can bind to diverse HLA alleles and also because they include conserved MSP2 sequences. Immunisation with a vaccine construct incorporating the sequences present in these peptides could thus be expected to be immunogenic in a high percentage of individuals and lead to the establishment of memory T-cells, which can be boosted through natural infection.
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PMID:Human T-cell recognition of synthetic peptides representing conserved and variant sequences from the merozoite surface protein 2 of Plasmodium falciparum. 943 61

When mice previously cured of a Plasmodium vinckei infection were subsequently infected with Salmonella enteritidis the course of bacterial infection was significantly retarded, showing increased survival duration as compared with control infections in naive mice. Moreover, on stimulation with lipopolysaccharide and/or interferon-gamma, spleen cells from malaria-cured mice showed an increased capacity to produce tumor necrosis factor, interleukin 6, and reactive nitrogen intermediates as compared with spleen cells from naive mice. However, no significant variation in the capacity of spleen cells to release reactive oxygen intermediates was observed between previously malarious and naive mice. The most significant increases were observed in the capacity for reactive nitrogen intermediate production after P. vinckei malaria. These results suggest that the observed protection of mice against salmonellosis in the convalescent phase after malaria may be mediated by nitric oxides.
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PMID:Protection of mice previously infected with Plasmodium vinckei against subsequent Salmonella enteritidis infection is associated with nitric oxide production capacity. 949 29

Coccidiosis is the most important parasitic infection in poultry worldwide and also causes problems in cattle, sheep and goats. Control is largely limited to good husbandry and prophylactic chemotherapy using a range of drugs against which resistance is rapidly acquired. Attempts at vaccination using conventional vaccines have been disappointing and there is now a need for a new approach. Research into the immunology of coccidiosis has lagged behind that of other sporozoans and there are useful lessons that might be learned from studies on toxoplasmosis, cryptosporidiosis, theileriosis and malaria. In these infections the emphasis has turned to the cytokine network that drives the response towards protection. Central to these studies are the roles of interferon-gamma, interleukin-12 and activated macrophages with the involvement of nitric oxide in parasite killing. Cytotoxic T cells have also increasingly been implicated. Research has shown that different immune responses can be elicited by manipulating the cytokine system and these new concepts can be applied to the design of peptide or recombinant vaccines, and the possibilities of developing such vaccines against coccidiosis will be discussed.
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PMID:Control of coccidiosis: lessons from other sporozoa. 950 43

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.
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PMID:Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. 954 83

The potential of building multi-cytotoxic T lymphocyte (CTL) epitope antigens in combination with the nucleic acid immunization technology is explored for development of acquired immunodeficiency syndrome (AIDS) and malaria vaccines. A novel minimal vector pTH for direct gene transfer was constructed for efficient expression of vaccine antigens and used as a vehicle for human immunodeficiency virus (HIV)- and Plasmodium falciparum-derived polyepitope genes. Two murine epitopes were included into these constructs to allow for testing of vaccine immunogenicity in small animals. The results showed that a single DNA injection generated CTL responses in all 15 vaccinated mice. The elicited CTL precursor frequencies were estimated in an interferon-gamma (IFN-gamma)-based ELISPOT assay and found to be an average of 300 (range 4-1346) peptide-responding cells per 10(6) splenocytes.
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PMID:DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. 960 66

The molecular events controlling sporozoite invasion and exo-erythrocytic (EE) development within hepatocytes are largely not understood, and EE parasites are probably better defined immunologically than biologically. The observation that the Plasmodium falciparum sporozoite antigen TRAP (thrombospondin-related anonymous protein) contains multiple adhesive domains that recognize endothelial and hepatocyte receptors indicates that, like leucocyte passage across capillaries, sporozoite invasion probably involves a co-ordinated interaction between sporozoite and hepatic molecules. The parallel with leucocyte extravasation is strengthened by the finding that TRAP contains a functional, integrin-like, I domain. EE parasites are an important target of immunity elicited by irradiated sporozoites, and much current effort is focused on developing malaria vaccines targeting EE parasites. Only one EE-specific antigen, liver-stage antigen 1 (LSA-1), is known to be expressed during EE development and may contribute to protective immunity elicited by irradiated P. falciparum sporozoites. In a study in Papua New Guinea, resistance to P. falciparum infection correlated with CD8+ T-cell interferon-gamma responses to an LSA-1 epitope that contains an HLA A11-restricted sequence. Since A11 is > 40% frequent in this population it is reasonable to suggest that, as with B53 responses to LSA-1 in The Gambia, P. falciparum has driven genetic selection of certain HLA haplotypes, as proposed by Haldane nearly 50 years ago. LSA-1 is thus an important vaccine candidate, and is being expressed in bacterial and phage vectors.
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PMID:Biology of malarial liver stages: implications for vaccine design. 968 93


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