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)

Spleen-intact and splenectomized Saimiri monkeys of Guyanan origin were examined for their potential suitability for Plasmodium falciparum protection studies. The animals could be readily infected with adapted strains of P. falciparum (Indochina 1/CDC and Uganda Palo Alto FUP strains), but spontaneously recovered without drug treatment and without development of severe clinical disease. In intact animals, peak parasitemia prior to recovery generally ranged from 0.1% to 10%, whereas in splenectomized animals the peak parasitemia was generally higher so that some animals were given drug treatment to assist in recovery from infection. In reinfection studies, previously infected spleen-intact monkeys demonstrated sterile immunity to the homologous parasite strain but not to a heterologous strain. However, in monkeys infected with the heterologous strain, the peak parasitemia was less than in the first infection and of shorter duration. Splenectomized animals did not demonstrate sterile immunity although the peak parasitemia achieved was less than in the previous infection of each of these monkeys. While the lack of major clinical disease indicated that these monkeys did not provide a good animal model for human malaria, the development of protective immunity was consistent with a useful role in evaluating candidate vaccine antigens.
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PMID:Plasmodium falciparum infection of splenectomized and intact Guyanan Saimiri monkeys. 806 23

The induction of T helper cell subsets during the course of non-lethal or lethal blood-stage Plasmodium chabaudi AS infection was investigated using inbred strains of mice which differ in the level of resistance to this intraerythrocytic parasite. Resistant C57Bl/6 mice experience a non-lethal course of infection characterized by moderate levels of both parasitaemia and anaemia and resolution of primary acute infection by 4 weeks, while susceptible A/J mice experience lethal infection with fulminant parasitaemia and severe anaemia. T helper subset function was assessed during infection by determining the kinetics of spleen cell production in vitro of the Th1-derived cytokine, interferon-gamma (IFN-gamma), and of the Th2-derived cytokine, IL-5, using sandwich ELISAs. Spleen cells from resistant C57Bl/6 mice were found to produce high levels of IFN-gamma within 1 week of infection in response to both the mitogen concanavalin A (Con A) and malaria antigen. Furthermore, CD4+ T cells were found to be the source of IFN-gamma while both CD4+ and CD8+ T cells were found to produce IL-5. Decreased IFN-gamma production after day 10 was concomitant with significant production of IL-5 between 2 and 3 weeks post infection. In contrast, spleen cells from susceptible A/J mice produced high levels of IL-5 within the first week of infection. In addition, these animals were found to have high serum levels of IL-5. These results, thus, confirm previous observations that resolution of primary blood-stage P. chabaudi infection occurs by sequential activation of Th1 CD4+ T cells followed by activation of the Th2 subset, and in addition, suggest that induction of a strong Th2 response early in infection may lead to a severe and lethal course of malaria.
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PMID:Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. 809 4

The epidemiology of malaria was investigated in a high rainfall, forested area of southern Sierra Leone. The prevalence rates of P. falciparum, P. malariae and P. ovale in 0-7 year old children, during two surveys conducted over a 12-month period, averaged 61%, 12% and 1% respectively. Groups of febrile children had higher prevalence rates than afebrile groups. Overall, gametocyte rates were approximately one fifth of the trophozoite rates. Malaria accounted for 27% of deaths, as did malnutrition, although no malaria associated deaths occurred in 0-12 month olds. Spleen rates were similar to P. falciparum prevalence rates, and the size did not appear to be related to parasite load at the time of the surveys. Packed cell volumes had normal distributions, with a lower mode after the peak prevalence period. Chloroquine usage increased during the post-rains period compared to the pre-rains period.
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PMID:The epidemiology of malaria in southern Sierra Leone. 823 97

Spleen and lymph node cells from Plasmodium yoelii 17X-infected, C57BL/6 (B6), and DBA/2 (D2) mice were cultured in vitro with parasite antigens. The ability of these cells to proliferate was quantified by uptake of [3H]thymidine and ELISA was used to measure secretion of IFN-gamma and IL-5. B6 mice are relatively susceptible to P. yoelii 17X infection compared to D2 mice. Susceptible mouse strains develop higher levels of parasitemia, become more anemic, and take longer to resolve their infections than do resistant strains. Following splenectomy, D2 mice resisted P. yoelii 17X infections as well as did sham-operated controls, but splenectomized B6 mice failed to resolve their infections and all died. Spleen cells from infected mice of either strain were activated in vitro as evidenced by their proliferation in the absence of exogenous antigen. When malaria antigen was added to these cultures, cells from resistant D2 mice responded strongly with increased proliferation, whereas cells from susceptible B6 mice responded weakly, and on Day 14 postinfection, responses were actually suppressed. Mesenteric lymph node cells from infected B6 and D2 mice did not proliferate in the presence or absence of P. yoelii 17X antigen unless the spleen was removed. Following splenectomy, mesenteric lymph node cells from D2 mice, but not B6 mice, proliferated strongly compared to cells from sham-operated controls. IFN-gamma and IL-5 production from spleen and lymph node cells was measured following in vitro stimulation with P. yoelii 17X antigen. Spleen cells from D2 mice produced levels of IFN-gamma increased over those of cells from B6 mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmodium yoelii: cellular immune responses in splenectomized and normal mice. 851 76

The prevalence of Plasmodium falciparum in a cohort of over 900 nought to seven-year-old children living in a rural area of Sierra Leone was found to be approximately 61%, both before and after the rainy season. Plasmodium malariae rates measured in the same children were approximately 12%, and P. ovale rates averaged about 1%. Spleen rates averaged 44% for the two surveys; the age prevalence spleen profiles closely matched those for P. falciparum. The overall gametocyte rates for both P. falciparum and P. malariae were roughly one fifth of the prevalence rates for the asexual parasites. However, whilst there was no difference between the P. falciparum gametocyte rates at the two surveys, the P. malariae rate was significantly higher post-rains when compared with the pre-rains result. Spleen size did not increase with increased parasite density. There was a statistically significant difference between the geometric mean P. falciparum trophozoite densities of febrile and afebrile children both before and after the rainy season, but there was little seasonal difference in the means for the febrile children or in those for the afebrile children. Antimalaria antibody levels, measured by ELISA and IFAT, showed no significant differences at either survey. The levels found were high for all age groups, indicating that exposure to malaria begins at birth. Our results indicate that, in the area studied, malaria is hyperendemic and is probably transmitted perennially.
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PMID:Malaria in a rural area of Sierra Leone. II. Parasitological and related results from pre- and post-rains clinical surveys. 856 20

We investigated the induction of T-helper cell subsets during the course of lethal or nonlethal bloodstage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythrocytic parasites. C57BL/6 mice infected with the nonlethal variant (PyNL) showed a moderate level of parasitemia and resolution of primary acute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN-gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells obtained from mice infected with PyL within the 1st week of infection produced high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mice at the same time at which the in vitro IL-10 response peaked. In contrast, spleen cells from mice infected with PyNL failed to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice infected with the lethal variant were a major source of IL-10, although non T-cells were also involved in the production of IL-10 during this malaria infection. In addition, the initial burst of IL-10 in response to malaria antigens was seen concomitantly with the production of IFN-gamma within the 1st week of infection. These results indicate that both Th1 and Th2 subsets of T-helper lymphocytes are activated during infection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.
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PMID:Production of interleukin 10 during malaria caused by lethal and nonlethal variants of Plasmodium yoelii yoelii. 873 75

A cardinal feature of malaria, splenomegaly, is usually absent in adult patients who have already suffered from falciparum malaria or who are natives of an endemic falciparum zone. This is an attribute of the past episode of clinical or sub-clinical malaria which usually results in regression of the splenic size to below-normal. An ultrasonographic evaluation of spleens was done in 90 healthy adult males, who had suffered from vivax (n = 28) or falciparum (n = 25) malaria in the past, except the controls (n = 22) and natives from an endemic falciparum area (n = 15) who never suffered from malaria. Their ultrasonographic details of spleens, including the size, were compared. Besides other conspicuous differences in the ultrasonographic picture, spleen size was found significantly decreased (p < 0.01) in the group who had been affected by P. falciparum malaria; the smallest measured 7.8 cms. In P. vivax group the decrease was not significant (p < 0.1), but was highly significant in inhabitants of endemic falciparum region (p < 0.001). The present study establishes the 'Small Spleen' and looks at echotexture pattern variations thereof for the first time.
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PMID:The 'small spleen' in malaria. 928 11

The effect of malaria parasitaemia on spleen size and anaemia in 1,905 pregnant women in Jos Plateau highlands, Bauchi Savannah plains and Ethiope river basin of Nigeria was evaluated. The overall spleen rates in Jos Plateau, Bauchi and Ethiope were 15, 23, 16.33 and 10.71% respectively. Higher cases of palpable spleen were detected in pregnant women than non-pregnant controls. Spleen rates also showed seasonal variation, but not very significant. Malaria prevalence rates were higher than spleen rates. In all three study sites, parasitaemic pregnant women had significantly lower haemoglobin values than malaria negative mothers, especially among primigravids. However, there was no constant association between higher parasite density and splenomegaly, since few cases of enlarged spleens were also recorded among subjects with low parasitaemia. Severe anaemia was predominant among parasitaemic pregnant women with high spleen classes.
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PMID:Malaria in pregnancy in Nigerians: seasonality and relationship to splenomegaly and anaemia. 929 70

The pathophysiological impact of infections with chloroquine-susceptible (CQS) and chloroquine-resistant (CQR) strains of Plasmodium berghei in Mastomys natalensis was studied with respect to changes in polyamine profiles in various tissues. Both CQS and CQR infections produced similar changes in polyamine profiles of various tissues. Maximum increase was recorded in spleen followed by liver and lungs. Renal, cardiac and cerebral tissues did not register significant changes. An increase in spermidine level was more prominent as compared to putrescine and spermine, leading to an overall increase in spermidine/spermine ratio. This ratio is an important index of cellular proliferation. Liver did not show considerable change in the activities of ornithine decarboxylase and S-adenosyl methionine decarboxylase, the regulatory enzymes of the polyamine biosynthetic pathway. Spleen however, registered marked induction of both the enzymes which was more prominent in the CQS infection than CQR. Normal erythrocytes contained traces of polyamine while the erythrocytes loaded with P. berghei parasites exhibited appreciably higher polyamine levels. Spermidine was detected in about five-fold higher concentrations than putrescine and spermine which were detected in equimolar levels. Again, CQS as well as CQR P. berghei, exhibited qualitatively and quantitatively similar polyamine profiles thus ruling out a role of polyamines in CQ-resistance in malaria.
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PMID:Polyamine metabolism in various tissues during pathogenesis of chloroquine-susceptible and resistant malaria. 941 68

Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used a novel methodology to synthesize and fully characterize multiple antigen peptide (MAP) conjugates containing protective epitopes from Plasmodium falciparum and evaluated their immunogenicity in four different strains of mice. A di-epitope MAP (T3-T1) containing two T-cell epitopes of liver stage antigen-1 (LSA-1), a di-epitope MAP containing T-cell epitopes from LSA-1 and from merozoite surface protein-1, and a tri-epitope MAP (T3-CS-T1) containing T3-T1 and a potent B-cell epitope from the circumsporozoite protein central repeat region were tested in this study. Mice of all four strains produced peptide-specific antibodies; however, the magnitude of the humoral response indicated strong genetic restriction between the different strains of mice. Anti-MAP antibodies recognized stage-specific proteins on the malaria parasites in an immunofluorescence assay. In addition, serum from hybrid BALB/cJ x A/J CAF1 mice that had been immunized with the tri-epitope MAP T3-CS-T1 successfully inhibited the malaria sporozoite invasion of hepatoma cells in vitro. Spleen cells from immunized mice also showed a genetically restricted cellular immune response when stimulated with the immunogen in vitro. This study indicates that well-characterized MAPs combining solid-phase synthesis and conjugation chemistries are potent immunogens and that this approach can be utilized for the development of subunit vaccines.
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PMID:Immunogenicity of well-characterized synthetic Plasmodium falciparum multiple antigen peptide conjugates. 1144 64


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