Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system. Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6, lymphotoxin (LT), interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma in vitro following stimulation with P. falciparum antigen. We conclude that soluble IL-2R is a useful marker of disease severity independently of the association with levels of parasitaemia, and that functional regulation of different lymphocyte subsets occurs during acute malaria episodes.
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PMID:Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria. 814 74

Antibody titers and lymphocyte responses to synthetic peptides corresponding to repeated amino acid sequences of the 3' and 5' regions of Pf155/ring-infected erythrocyte surface antigen (RESA) were studied in two groups of Thai subjects, soldiers (Rangers), and villagers who differed in their history of malaria exposure. The frequency of Pf155/RESA seropositivity was similar in the two groups while the frequency of high titer antibody was significantly greater in villagers than in Rangers. Lymphocyte responsiveness in vitro to all Pf155/RESA peptides was infrequent for both groups although half of the subjects studied responded to crude Plasmodium falciparum asexual blood stage malaria antigen (MA). Among responders, Pf155/RESA peptides elicited lymphocyte responses in which proliferation and interferon-gamma (IFN-gamma) production were not associated, whereas with MA, the two responses were associated. The MA-stimulated lymphocyte proliferation and IFN-gamma production for both groups of volunteers appeared to be independent of antibody titer. In this study, antibody, but not lymphocyte, responses to Pf155/RESA peptides were shown to reflect differences in prior exposure and levels of acquired immunity to falciparum malaria.
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PMID:Lymphocyte responses to Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) peptides in individuals with naturally acquired Plasmodium falciparum malaria. 816 54

The design of vaccine strategies in general, and those for malaria in particular, need to take into account the balance of T helper subsets (TH) they induce. The TH1 cells, which secrete interferon-gamma and interleukin-2 (IL-2), are associated with cell-mediated immunity (CMI), rather than humoral responses, and afford protection against intracellular infections, including those caused by parasites. In contrast, the TH2 cells secrete IL-4, IL-5, and IL-10, elicit high titer antibody responses, provide poor CMI, and are often correlated with susceptibility to infection. Depending on the type of TH cell bias required, it is possible to manipulate the immune response to a protein/peptide by 1) using different adjuvants, 2) conjugating the protein to various carriers, 3) immunizing in the presence of cytokines, or 4) using alternative routes of administration. To apply these approaches to malarial vaccines, it is necessary to identify which stage(s) of the parasite to target and what type of TH cell bias is protective against that particular stage. We favor using carriers such as Brucella abortus, which focus the antigen on a specific particle and which can trigger a TH1 cell response.
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PMID:The potential for recruiting immune responses toward type 1 or type 2 T cell help. 817 30

Volunteers immunized with gamma-irradiated Plasmodium falciparum sporozoites serve as the gold standard for protective immunity against mosquito-borne malaria transmission and provide a relevant model for studying protective immune effector mechanisms. During a 7-12 month period, we immunized four volunteers via the bites of irradiated, infected mosquitoes. Following these exposures to attenuated sporozoites, all four volunteers developed antibodies to sporozoites as measured by an immunofluorescence assay and by an enzyme-linked immunosorbent assay using the circumsporozoite (CS) protein repeat-based molecule R32LR as capture antigen. Three volunteers also developed antibodies against the nonrepeating (flanking) regions of the CS protein; the level of these antibodies paralleled the serum activity to inhibit sporozoite invasion of hepatoma cells in vitro. These three volunteers were protected against malaria transmitted by the bites of five infected mosquitoes. Two of these protected volunteers received additional immunizing doses of irradiated sporozoites and were subsequently protected against challenge with a heterologous P. falciparum clone. No detectable fluctuations were observed in circulating levels of tumor necrosis factor, interferon-gamma, or interleukin-6 during the course of this study. Analysis of the humoral and cellular immune responses of these protected volunteers is expected to yield important clues to additional targets of immunity against the pre-erythrocytic stages of malaria parasites.
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PMID:Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. 835 78

A resurgence of falciparum malaria occurred in the central highlands of Madagascar in the 1980s and was responsible for an outbreak in 1986-1987. Since 1989, transmission has decreased dramatically. In April 1991, we investigated the humoral and cellular immune responses of 53 inhabitants of the village of Manarintsoa to six synthetic peptides that reproduced the major B and/or T cell epitopes of the Pfl 55/ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. The presence of RESA peptide-reactive T cells was assessed by lymphocyte proliferation assay as well as by detection of in vitro production of interferon-gamma and interleukin-2. The mean values of these cellular responses were low, and the results obtained in these three tests showed no correlation. Twenty-seven subjects presented with anti-RESA antibodies as detected by modified immunofluorescent assay, but the mean levels of anti-peptide antibodies were low. When compared with data obtained in January 1988 from the same subjects with three of the six peptides, the present data demonstrated a decrease in the response to these peptides in terms of both proliferative response and mean antibody titers. The mean values of anti-RESA antibodies remained unchanged. The fact that cellular and humoral responses to the major Pfl 55/RESA epitopes decreased but did not disappear probably reflects both the remainder of the acquired immunity resulting from the 1986-1987 malaria outbreak, and its conservation by the very low level of transmission since 1989.
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PMID:Human immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) after a decrease in malaria transmission in Madagascar. 847 Jul 78

The in vitro production of reactive nitrogen intermediates (RNI) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. Malaria antigen, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) induced RNI production in macrophages in a dose-dependent way. RNI production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with IFN-gamma and/or TNF. RNI production induced by either IFN-gamma or malaria antigen or a combination of the two was suppressed by pentoxifylline in a dose-dependent manner. Pentoxifylline did not significantly influence TNF-induced RNI production. L-N-monomethyl arginine reduced malaria antigen, IFN-gamma and TNF-induced RNI production when these reagents were used in combination or alone. An anti-TNF monoclonal antibody (mAb) reduced IFN-gamma-induced RNI production, but did not significantly alter the malaria antigen-induced RNI synthesis by macrophages. The influence of inhibitors of nitric oxide synthase, L-N-monomethyl arginine and N omega-nitro-L-arginine, was studied in experimental cerebral malaria. They did not exert any significant effect on the development of cerebral malaria in Plasmodium berghei ANKA-infected CBA/J mice.
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PMID:Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria. 847 17

The production of reactive oxygen intermediates (ROI) by host macrophages has long been recognized as an important defense mechanism against microorganisms. More recently, reactive nitrogen intermediates (RNI), also produced by activated macrophages, have been shown to be part of the host's first line of defense against malaria. In the present in-vitro study we have investigated the effects of antimalarial drugs on RNI production by murine macrophages stimulated by interferon-gamma (IFN-gamma) and/or malaria antigen, and on ROI production induced by phorbol myristate acetate. At concentrations exceeding the peak serum levels achieved with therapeutic dosages, chloroquine, in a dose-dependent manner, inhibited IFN-gamma- and malaria antigen-induced RNI production. Quinine, at a concentration of 10 mg/L also caused a significant reduction in IFN-gamma and malaria antigen-induced RNI synthesis; this concentration was well within the therapeutic range. High concentrations of artelinate significantly inhibited IFN-gamma-induced RNI production but clindamycin had no effect on RNI synthesis. In contrast, halofantrine, in concentrations attainable with therapeutic dosages, significantly enhanced IFN-gamma-induced RNI production. ROI production by murine macrophages was unaffected by the antimalarial drugs over the same concentration ranges. It remains to be determined whether these in-vitro effects of antimalarial drugs on RNI production also influence the clinical and parasitological response in patients with malaria.
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PMID:Interference by antimalarial drugs with the in-vitro production of reactive nitrogen intermediates by murine macrophages. 848 72

Recombinant rat interferon-gamma (rrIFN-gamma) was tested for its antimalarial activity in three different models of Plasmodium chabaudi-blood stage malaria. Doses ranging from 1 x 10(4) to 1 x 10(5) U of rrIFN-gamma were used in each model. In BALB/c mice (lethal infection), prophylactic treatment with daily intraperitoneal (i.p.) injections reduced parasitemia and delayed mortality. In contrast, subcutaneous administration of rrIFN-gamma was inefficient, as was curative schedule of i.p. administration. Euthymic Fischer rats, which develop an acute and resolutive infection, were partly protected by i.p. prophylactic administration of rrIFN-gamma. Parasitemia was reduced without being lengthened, resulting in a marked decrease in parasite burden. Subcutaneous administration was less efficient whereas curative schedule was not. Athymic (nude) Fischer rats which present a longlasting and stable infection were treated with prophylactic and curative schedules of i.p. administration of rrIFN-gamma. In each case, rrIFN-gamma-treated nude rats, as control nude rats, were unable to resolve their chronic infection. The conditions required to obtain a beneficial effect are thus restrictive for a therapeutic use in humans. Moreover, these results show that, despite the fact that IFN-gamma is considered as a major component of the immune response, this cytokine alone is not sufficient to induce the totality of the effector mechanisms necessary to cure malarial infections.
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PMID:IFN-gamma treatment of rodents infected with erythrocytic stages of Plasmodium chabaudi: differential effects according to the immunological status. 850 41

To investigate the mechanisms underlying the increased susceptibility to malaria in pregnant women, we determined the level of malaria-specific immunity in primigravidae. Humoral and cellular in vitro responses to unpurified (a crude schizont extract and a gametocyte preparation) and purified (affinity-purified Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis, and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant women from a semirural area of Cameroon. In vitro cellular responses were investigated in terms of lymphocyte proliferation, as well as production of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and IL-4. Cells from primigravidae exhibited a reduced proliferative response to schizont and gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2 response to Pf155/RESA was reduced. Interleukin-4 and IFN-gamma production did not appear to be affected in primigravidae. Antibody levels were also similar between pregnant and nonpregnant women. Our results underline the importance of examining several parameters of T cell activation with different types of antigens for a correct evaluation of the ability of lymphocytes to respond to malaria.
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PMID:Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune responses to Plasmodium falciparum blood-stage antigens. 856 Dec 63

We have recently shown that some squirrel monkeys (Saimiri sciureus) develop cerebral malaria when experimentally infected with asexual blood stage forms of different Plasmodium falciparum isolates. Since cerebral malaria is neither an inconsistent nor predictable event, several clones of endothelial cells isolated from the squirrel monkey brain microvasculature have been developed. Infected red blood cell (IRBC) adherence involved the knobs and direct membrane interactions through pseudopodes and microvilli on the Saimiri brain endothelial cell (SBEC) surface, similar to that observed with both brain microvascular endothelial cells from a patient who died of cerebral malaria and the rhesus monkey/P. coatneyi cerebral malaria model. The involvement of pseudopodes and microvilli increase the endothelial cell surface for the attachment of IRBCs; however, they are already present before the SBECs are exposed to IRBCs. With some SBEC phenotypes, embedding of IRBCs into the cytoplasma membrane of the endothelial cell was observed, resulting in an extremely close apposition of both SBEC and IRBC membranes during the adherence process. Once IRBCs are adherent, particularly for the embedding type, heterocellular communication-like structures between the cells become apparent. The upregulation of CD36 and intercellular adhesion molecule-1 by soluble recombinant (sr)-tumor necrosis factor-alpha or sr-interferon-gamma did not modify the IRBC interactions with SBECs at the ultrastructural level. The study shows further that the observed differences of IRBC adherence are due to unidentified phenotypic differences of SBECs rather than to a parasite isolate or particular endothelial cell receptor-associated phenomenon. Exploring P. falciparum IRBC cytoadherence in the squirrel monkey using a homologous physiologic target cell model in vitro should be useful for the evaluation of vaccine strategies and drugs to prevent human cerebral malaria.
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PMID:Ultrastructural aspects of Plasmodium falciparum-infected erythrocyte adherence to endothelial cells of Saimiri brain microvasculature. 861 43


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