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

Relationships of S. haematobium, hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth, S. haematobium and hookworm were common and malaria was endemic. All children with light-moderate S. haematobium infections (1-500 eggs/10 ml adj) in 4 schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 201) groups, treated, and examined again 6 months later (Exam 2). An additional 19 heavily infected children (HIT group greater than 500 eggs/10 ml adj) were treated immediately after Exam 1 and also followed. The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group. The MIT group gained significantly (P less than 0.001) more than the MIP group in weight (0.8 kg), percent weight for age (2.3 percentage points), weight for height squared (0.04 units), arm circumference (0.4 cm), percent arm circumference for age (1.7 percentage points) and in triceps and subscapular skinfold thicknesses. In addition, the placebo group showed statistically significant decreases between exams in percentage weight for age, percent arm circumference for age, both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationships of Schistosoma haematobium, hookworm and malarial infections and metrifonate treatment to growth of Kenyan school children. 393 25

Relationships between hemoglobin level and S. hematobium, hookworm, and malarial infection before and six months after metrifonate treatment were studied in Kenyan primary school children in an area where anemia, S. hematobium and hookworm are common (prevalences 61%, 46%, and 95%, respectively) and malaria is holoendemic. The mean hemoglobin level in children from one school, both with and without S. hematobium infection (n = 250), was significantly lower in children with higher S. hematobium egg counts, heavier hookworm infections, positive Plasmodium slides, and larger spleens. All children with light-moderate S. hematobium infection (1-500 eggs/10 ml adj) in four schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 202) groups, treated, and examined again six months later (Exam 2). Hemoglobin levels rose significantly in both groups between exams, but the rise in the MIT group was 30% higher than in the MIP group (1.3 vs. 1.0 g/dl, P less than 0.014). The increase in hemoglobin level in the MIT group was significantly and positively correlated with decreases between exams in S. hematobium and hookworm egg counts and with higher malarial parasite counts at Exam 1 (Pearson r's 0.21, 0.20, 0.20, respectively, P less than 0.01). A stepwise multiple regression equation using hemoglobin rise between exams as the dependent variable showed that decreases in S. hematobium and hookworm egg counts were equally important determinants of hemoglobin rise and that malarial parasite count was almost as important as the changes in intensities of the helminth infections. These results show that treatment for S. hematobium with metrifonate can increase hemoglobin levels in children in an area where S. hematobium and anemia are common. They also emphasize the importance of measuring multiple parasitic infections and using multivariate statistical techniques such as multiple regression analysis in order to define the relationships between parasitic infections and morbidity.
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PMID:Relationships of Schistosoma hematobium, hookworm and malarial infections and metrifonate treatment to hemoglobin level in Kenyan school children. 400 67

A characteristic feature of malaria infection is the occurrence of periodic bouts of fever. Experimental and clinical studies have strongly implicated inflammatory cytokines, like tumour necrosis factor (TNF), in the induction of these intermittent fevers [Clark et al., Infect Immunol 32:1058-1066, 1981; Clark et al., Am J Pathol 129:192-199, 1987; Karunaweera et al., Proc Natl Acad Sci USA 89:3200-3203, 1992], but the malaria-specific metabolite(s) which induce the production of such endogenous pyrogens have not yet been fully characterized. It is well known that during the course of malaria infection, a unique schizont component, alternatively referred to as "malaria pigment" or hemozoin, is released along with merozoites as the host erythrocyte bursts [Urquhart, Clin Infect Dis 19:117-131, 1994]. We have recently determined that the core structure of hemozoin comprises a novel insoluble polymer of heme units linked by iron-carboxylate bonds [Slater et al., Proc Natl Acad Sci USA 88:325-329, 1991; Slater et al., Nature 355:167-169, 1992]. We now report that purified native, as well as chemically synthesized, hemozoin crystals potently induce the release of several pyrogenic cytokines, including TNF, MIP-1 alpha, and MIP-1 beta, from murine macrophages and human peripheral blood monocytes in vitro. Also, intravenous administration of chemically synthesized preparations of hemozoin to anaesthetized rats results in a marked drop in body temperature. A similar drop in body temperature is observed following the intravenous injection of other well-characterized pyrogenic cytokines (e.g., TNF) which are known to induce a fever response in awake animals, and is thought to reflect the inability of rats to appropriately regulate their body temperature while anaesthetized. As a consequence of its ability to induce pyrogenic cytokines in vitro, and thermal dysregulation in vivo, we propose that this unique parasite metabolite is an important pyrogen released by malaria parasites at schizogomy, which acts by eliciting the production of a group of potent endogenous pyrogens, which include MIP-1 alpha and MIP-1 beta, as well as TNF, in macrophages.
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PMID:Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo. 758 61

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.
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PMID:Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria. 760 66

Chemokines are small pro-inflammatory peptides that are best known for their leukocyte-chemoattractant activity. The cloned leukocyte chemokine receptors, interleukin 8 receptor (IL-8R) types A and B and the macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES receptor, are related by sequence and chemokine binding to two herpesvirus products, and to the Duffy antigen that mediates erythrocyte invasion by the malaria-causing parasite Plasmodium vivax. Here, Sunil Ahuja, Ji-Liang Gao and Philip Murphy suggest that, in addition to the activation of leukocytes, chemokines may be important in the function of erythrocytes and, through molecular mimicry, in microbial pathogenesis.
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PMID:Chemokine receptors and molecular mimicry. 806 75

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.
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PMID:Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). 992 12

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.
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PMID:Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression. 1259 7

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1 beta concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1 beta than HIV-positive PM-negative women. The MIP-1 alpha level was not altered in association with either infection. The IVB plasma levels of MIP-1 alpha and MIP-1 beta positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1 beta compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1 beta and MIP-1 alpha levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1 beta level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1 beta was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma.
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PMID:Levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta in intervillous blood plasma samples from women with placental malaria and human immunodeficiency virus infection. 1285 96

Chemokine production has been associated with the immunopathology related to malaria. Previous findings indicated that hemozoin (HZ), a parasite metabolite released during schizogeny, might be an important source of these proinflammatory mediators. In this study we investigated the molecular mechanisms underlying HZ-inducible macrophage (Mphi) chemokine mRNA expression. We found that both Plasmodium falciparum HZ and synthetic HZ increase mRNA levels of various chemokine transcripts (MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2, and MCP-1/CCL2) in murine B10R Mphi. The cellular response to HZ involved ERK1/2 phosphorylation, NF-kappaB activation, reactive oxygen species (ROS) generation, and ROS-dependent protein-tyrosine phosphatase down-regulation. Selective inhibition of either IkappaBalpha or the ERK1/2 pathway abolished both NF-kappaB activation and chemokine up-regulation. Similarly, blockage of HZ-inducible Mphi ROS with superoxide dismutase suppressed chemokine induction, strongly reduced NF-kappaB activation, and restored HZ-mediated Mphi protein-tyrosine phosphatase inactivation. In contrast, superoxide dismutase had no effect on EKR1/2 phosphorylation by HZ. Collectively, these data indicate that HZ triggers ROS-dependent and -independent signals, leading to increased chemokine mRNA expression in Mphi. Overall, our findings may help to better understand the molecular mechanisms through which parasite components, such as HZ, modulate the immune response during malaria infection.
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PMID:Hemozoin induces macrophage chemokine expression through oxidative stress-dependent and -independent mechanisms. 1561 Dec 73

Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities.
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PMID:Pregnancy outcome and placenta pathology in Plasmodium berghei ANKA infected mice reproduce the pathogenesis of severe malaria in pregnant women. 1827 May 95


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