UMLS:C0024530 - FACTA Search

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

Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0-90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0-36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.
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PMID:A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. 1043 33

The kinetic profiles of soluble chondroitin-sulphate A (CSA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin were investigated in 17 patients hospitalized with Plasmodium falciparum malaria. The aim was to see if these circulating adhesion molecules could be considered as markers for the severity of P. falciparum malaria. The levels of all the adhesion molecules were found to be higher in the sera from all the malaria cases, both severe and uncomplicated, than in those from uninfected controls. The elevation in plasma CSA, reported for the first time, was statistically very significant (P = 0.00001). However, when severe cases were compared with the uncomplicated, there were no significant differences in the level of any of the receptors except ICAM-1, which was highest in those with the severe disease (P = 0.01). The absence of any significant correlation between the plasma concentration of CSA and malaria severity indicates that this adhesion molecule could not be used to predict the severity of malaria, although its role in sequestration of the parasites in pregnant women is well established.
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PMID:Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand. 1069 Feb 40

In Plasmodium falciparum-parasitized pregnant women, erythrocytes infected by mature stages of the parasite sequester into placental intervillous spaces. The presence of parasites in the placenta causes maternal anaemia and low birth weight of the infant. In-vitro studies suggest placental sequestration may involve the cytoadherence of infected erythrocytes to chondroitin sulphate A (CSA) and/or intercellular adhesion molecule 1 (ICAM-1) expressed by human placental syncytiotrophoblast. We identified P. falciparum receptors expressed on the surface of human syncytiotrophoblast using immunofluorescence of placental biopsies from Cameroon, a malaria-endemic area. In all placentas, a strongly positive staining was observed on the syncytiotrophoblast for CSA, but not for ICAM-1, vascular endothelium cell adhesion molecule-1, E-selectin, nor CD36. The cytoadherence ability of parasites from pregnant women and nonpregnant subjects was assessed on in-vitro cultured syncytiotrophoblast. Parasites from pregnant women bound to the trophoblast via CSA but not ICAM-1. Parasites from nonpregnant hosts either did not bind to the trophoblast culture or bound using ICAM-1. Our data support the idea that placental sequestration may result from cytoadherence to placental trophoblast and that pregnant women are parasitized by parasites that differ from parasites derived from nonpregnant host by their cytoadherence ability.
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PMID:Cytoadherence of Plasmodium falciparum-infected erythrocytes in the human placenta. 1076 Jan 85

Using an in vitro model of human lung endothelial cells, we studied different characteristics of Plasmodium falciparum isolates as potential factors for malaria severity in 2 Thai patient groups: 27 with complicated malaria and 42 with uncomplicated malaria. In regard to binding properties, no association existed between cytoadherence and rosette phenotypes (P = 0.1) and hypothrombocytemia increased the cytoadherence level (P = 0.007). Cytoadherence was significantly associated with malaria severity (P = 0.05) in contrast to rosette formation (P = 0.9). Intercellular adhesion molecule-1 and chondroitin-4-sulfate were major receptors of cytoadherence in those with complicated malaria compared with those with uncomplicated malaria (P < 10(-4)). Chondroitin-4-sulfate could act as a putative receptor for malaria complications in non-pregnant women. CD36 was the main receptor in patients with uncomplicated malaria (P < 10(-3)). Vascular cell adhesion molecule-1 and E-selectin played a minor role in 2 groups (P = 0.6). Qinghaosu derivatives were more efficient than other antimalarial drugs, but a positive correlation was observed between the 50% inhibitory concentrations of halofantrine and quinine and the number of adhesive parasitized red blood cells, suggesting their influence on cytoadherence.
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PMID:Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model. 1076 22

As a result of damaging endothelial cells (ECs), Mycobacterium leprae triggers the production of antibodies (Abs). These anti-EC Abs (AECAs) can be divided into two types. The first type nonspecifically reacts with components of the cytosol (CY) and can be detected by enzyme-linked immunosorbent assay (ELISA). The second specifically reacts with the EC membrane (MB) and requires fluorescence-activated cell sorter (FACS) analysis to be detected. The presence of both types of AECAs was determined in 68 leprosy patients. The ELISA was positive for 35 of them but also for 30 of 34 malaria patients and 17 of 50 healthy African controls. However, whereas FACS analysis showed MB reactivity in only three malaria patients and four controls, this reactivity was found in 27 leprosy patients, more of those having the lepromatous than the tuberculoid form. Specificity for MB, which we failed to absorb by incubation with CY lysates, predominated over that for CY in leprosy, unlike malaria, where the EC reactivity was restricted to the CY. Western blot analysis and two-dimensional electrophoresis revealed that calreticulin, vimentin, tubulin, and heat shock protein 70 were targeted by AECAs from leprosy patients, but other proteins remained unidentified. These auto-Abs, but not those from malaria patients, did activate ECs, as indicated by the E-selectin and intercellular adhesion molecule 1 upregulation, and/or induced them into apoptosis, as documented by four different methods. Our findings suggest that, in some but not all leprosy patients, AECAs may play a role in pathogenesis.
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PMID:Effects of anti-endothelial cell antibodies in leprosy and malaria. 1468 9

Plasmodium falciparum malaria remains a major public health hazard in sub-Saharan African children. While the factors that determine the variations in clinical outcome of a malaria have not been completely defined, both host and parasite factors, as well as the complex molecular interactions between them have been implicated. The cyto-adherent properties of the P. falciparum-infected red blood cells are considered as key properties in the pathogenesis of malaria and the polymorphisms of the host adhesion molecules could contribute to the severity of malaria. Clinical information and blood samples were collected from 223 children from Ibadan (south-west Nigeria), median age of 34.5 months, presenting with different clinical manifestations of malaria--clinically asymptomatic parasitism (ACP), acute uncomplicated malaria (UM) and severe malaria (SM)--as defined by WHO criteria. The polymorphisms of genes coding for four human adhesion molecules at six different loci (ICAM-1 exons 2, 4 and 6, E-selectin exon 2, CD36 exon 10, and PECAM exon 3) were studied. DNA samples were prepared for further genotyping of the six exons mentioned above by PCR-RFLPs using the appropriate restriction digests for each loci. The ICAM-1 exon 4 locus was monomorphic. All the other loci were at Hardy-Weinberg equilibrium (HWE). The E-selectin locus had very low heterozygosity (approximately 0.06) in contrast to the other loci under study (0.23-0.44). Once the data was further processed for covariates (age and parasite density) and taking as the reference category the ACP group, results show that in the presence of the G allele at the ICAM-1 exon 6 there is an increased risk (3.6 times) of severe malaria. As far as the T allele in the E-selectin exon is concerned, the number of sampled DNAs with the T allele within both the UM and SM categories is too low for drawing any relevant conclusion at this stage. In conclusion, these results suggest that genetic polymorphisms at host adhesion molecules loci are an important variable in the susceptibility to severe malaria. Further studies of host loci are needed to further delineate which polymorphisms are associated with severe malaria and increase our knowledge of the biology of host-parasite interactions.
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PMID:Plasmodium falciparum malaria in south-west Nigerian children: is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria? 1600 39

The mechanism of blood-brain barrier breakdown in the complex pathogenesis of cerebral malaria is not well understood. In this study, primary cultures of porcine brain capillary endothelial cells (PBCEC) were used as in vitro model. Membrane-associated malaria antigens obtained from lysed Plasmodium falciparum schizont-infected erythrocytes stimulated human peripheral blood mononuclear cells (PBMC) to secrete tumor necrosis factor alpha. In co-cultivation with the brain endothelial cell model, the malaria-activated PBMC stimulated the expression of E-selectin and ICAM-1 on the PBCEC. Using electric cell-substrate impedance sensing, we detected a significant decrease of endothelial barrier function within 4h of incubation with the malaria-activated PBMC. Correspondingly, immunocytochemical studies showed the disruption of tight junctional complexes. Combination of biochemical and biophysical techniques provides a promising tool to study changes in the blood-brain barrier function associated with cerebral malaria. Moreover, it is shown that the porcine endothelial model is able to respond to human inflammatory cells.
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PMID:In vitro study of malaria parasite induced disruption of blood-brain barrier. 1610 59

Although the roles played by systemic tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta), and their upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin, in the pathogenesis of human cerebral malaria (CM) are well established, the role of local cytokine release, in the brain, remains unclear. Immunohistochemistry was therefore used to compare the expression of ICAM-1, VCAM-1, E-selectin, IL-1beta, TNF and transforming growth factor beta (TGF-beta) at light-microscope level, in cryostat sections of cerebral, cerebellar and brainstem tissues collected, post-mortem, from Ghanaian children. Among the 21 children investigated were 10 cases of CM, five of severe malarial anemia (SMA), one of purulent bacterial meningitis (PBM), two of non-central-nervous-system infection (NCNSI) and three children who had no infection (NI) when they died. Parasitised erythrocytes were detected in all of the sections from the cases of fatal malaria (CM and SMA), and sequestered leucocytes were present in most of the sections from the CM cases (but none of the sections from the SMA cases). Significantly elevated vascular expression of all three adhesion molecules investigated was detected in the brains of the 15 cases of fatal malaria and one of the cases of NCNSI (a child with Salmonella septicaemia), and in the malaria cases this showed highly significant co-localization with the areas of erythrocyte sequestration. In terms of the levels of expression of ICAM-1, VCAM-1 and E-selectin, there were, however, negligible differences between the CM and SMA cases. Although TGF-beta showed intravascular and perivascular distribution in all the subjects, its expression was most intense in the PBM case and the CM group. Only in the sections from the PBM and CM cases did TNF and IL-1beta show prominent brain parenchymal staining, in addition to the intravascular and perivascular staining seen in all subjects. The highest observed expression of each of the six antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation in the brain therefore appears to be a feature of fatal malaria and Salmonella sepsis, and in cases of fatal malaria is closely associated with leucocyte sequestration. In the present study, IL-1beta and TNF were only up-regulated in the brains of children with neurodegenerative lesions, whereas TGF-beta was present in all cases.
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PMID:High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria. 1621 98

To understand the mechanism of sequestration in the microvasculature of patients with falciparum malaria, we examined the patterns of expression of mRNAs for adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and tight junction molecules (occludin, vinculin, and ZO-1) in human umbilical vein endothelial cells (HUVECs) co-cultured with Plasmodium falciparum-parasitized red blood cells (PRBCs) in vitro. The PRBCs were collected from patients with uncomplicated, severe, or cerebral malaria (CM). Patterns of mRNA expression in HUVECs co-cultured with PRBCs were examined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Levels of mRNAs for all the three adhesion molecules increased with increased culture time within 3 h, regardless of the source of the PRBCs. In contrast, the patterns of mRNA expression for the tight junction molecules varied between the different co-cultures. When HUVECs were cultured with PRBCs from uncomplicated malaria patients, levels of mRNAs for tight junction molecules increased according to the culture time. HUVECs co-cultured with PRBCs from severe malaria patients showed no change in the mRNAs levels during 3 h of observation. When HUVECs were cultured with PRBCs from CM patients, levels of mRNAs for tight junction proteins decreased according to the culture time. Although the mechanisms underlying these phenomena are not clear, our results suggest that PRBCs can alter expression of tight junction proteins in endothelial cells at the site of sequestration and thereby influence disease severity.
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PMID:Down-regulation of tight junction mRNAs in human endothelial cells co-cultured with Plasmodium falciparum-infected erythrocytes. 1638 77

Scrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0.03) and the presence of eschar (P = 0.03), elevated white blood cell (WBC) count (P = 0.007), elevated lymphocyte (P = 0.007) and neutrophil counts (P = 0.015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0.03), the presence of lymphadenopathy (P = 0.033) and eschar (P = 0.03), elevated WBC (P = 0.005) and neutrophil counts (P = 0.0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0.03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar.
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PMID:Differential patterns of endothelial and leucocyte activation in 'typhus-like' illnesses in Laos and Thailand. 1850 34

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