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)

Collaborative studies have identified some genetic factors contributing to the development of severe forms of malaria and schistosomiasis. In Thailand, the TNF-alpha 5'-flanking region shows biallelic polymorphic sites at nucleotides -238, -308, -857, -863, and -1031, and seven alleles have been identified in patients from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly associated with cerebral malaria in populations from Karen (P < 0.0001, OR = 124.86) and ethnic Burma (P < 0.0001, OR = 34.50). In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA-DRB5*0101 allele and that of the IL-13 promoter A/A (IL-13P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively. Subjects with both genotypes had odds ratios (OR = 24.5) much higher than the sum of the ratios for each individual genotype (OR = 5.1, 95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR = 3.1 95% CI 1.5 - 6.5 for IL-13P- A/A). That the effects of the two susceptibility markers are synergistic rather than additive, strongly suggests that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.
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PMID:Genetic factors associated with development of cerebral malaria and fibrotic schistosomiasis. 1250 99

There is some evidence showing that genetic factors are involved in human susceptibility to parasitic diseases such as schistosomiasis and malaria. Studies have shown that the Nramp1 and H-2 genes are implicated in the control of Leishmania donovani infection in mice. We sought genetic loci involved in the control of susceptibility to visceral disease caused by L. donovani in humans. We studied 37 families with at least two affected sibs living in a village in eastern Sudan, where an outbreak of visceral leishmaniasis occurred between 1995 and 2000. The genetic markers located in five chromosomal regions containing candidate genes were typed: 2q35 (NRAMP1), 5q31-q33 (Th2 cytokine cluster), 6p21 (HLA/TNF-alpha), 6q23 (INFGRI) and 12q15 (INF-gamma). Linkage (multipoint lod-score=1.08; P=0.01) was observed for the 5'(CA) repeat polymorphism in the NRAMP1 promoter. This suggests that genetic variations of this gene affect susceptibility to visceral leishmaniasis in this population.
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PMID:Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region. 1261 57

A comparative study was carried out on cytokine and chemokine responses in a cerebral malaria (CM)-susceptible or -resistant strain of mice (C57BL/6 or BALB/c respectively) in Plasmodium berghei ANKA infection. C57BL/6 mice died by 10 days after infection when parasitemia was approximately 15-20% with cerebral symptoms, while BALB/c mice survived until week 3 after infection. Although both strains showed T(h)1-skewed responses on day 4 after infection, significantly higher levels of IFN-gamma, tumor necrosis factor (TNF)-alpha and NO were observed during the course of the infection in BALB/c, suggesting that T(h)1 responses are involved in the resistance. Interestingly, in the brain, both strains expressed IFN-inducible protein of 10 kDa (IP-10) and monocyte chemotactic protein (MCP)-1 genes as early as at 24 h post-infection, whereas some differences were observed between both strains thereafter, i.e. enhanced expression of RANTES in C57BL/6, and of IFN-gamma and TNF-alpha in BALB/c respectively. Moreover, the expression of IP-10 and MCP-1 genes in KT-5, an astrocyte cell line, was induced in vitro upon stimulation with a crude antigen of malaria parasites. These results suggest that the direct involvement of brain parenchymal cells takes place in response to plasmodial infection, providing a new aspect to analyze possible mechanisms of CM. This is the first report on the chemokine expression in neuroglial cells in response to malaria infection.
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PMID:Cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to Plasmodium berghei ANKA infection: early chemokine expression in the brain. 1269 63

We studied the impact of Plasmodium falciparum on nutritional status in a longitudinal cohort of 147 young men in western Kenya, where malaria transmission is intense and perennial. All volunteers received treatment to eradicate parasitemia and then provided weekly blood smears during a 16-week transmission season. We measured body mass index (BMI), pubertal development, frequency and density of parasitemia, and tumor necrosis factor (TNF)-alpha production by peripheral blood mononuclear cells. During early puberty, mean parasite density had a strong negative effect on the natural increase in BMI. Among older individuals, TNF-alpha production in response to malarial antigen predicted a significantly lower BMI (P<.03), equal to 4.6 kg for a man of average height. Our data indicate that burden of parasitemia has a detrimental effect on the nutritional status of early adolescents and that malaria may continue to influence nutritional status among older adolescents and adults via host elaboration of proinflammatory cytokines. These effects of malaria may have pervasive health and socioeconomic consequences in areas where malaria is endemic.
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PMID:Malaria is related to decreased nutritional status among male adolescents and adults in the setting of intense perennial transmission. 1287 Jan 28

Cerebral malaria is a severe complication of infection with Plasmodium berghei ANKA involving the Th1 cytokines TNF-alpha and IFN-gamma. Suppressor of cytokine signalling-1 (SOCS1) is an important component in the regulatory cascade controlling inflammatory responses and signalling through IFN-gamma. Contrary to the expectation that SOCS1-deficient mice, in which IFN-gamma responses are uncontrolled and which are more sensitive to IFN-gamma, may show heightened susceptibility, mice lacking SOCS1 were protected from cerebral malaria. Unlike the controls and despite similar parasitaemia, infected SOCS1 null mice showed no inflammation or haemorrhaging in the brains. Mice lacking SOCS1 exhibited decreased splenic cellularity and a reduced ratio of CD4 : CD8 lymphocytes, which were maintained during infection. However, the ratio of IFN-gamma to IL-4 mRNA expression during infection was similar in SOCS1 -/- and control mice suggesting that a dramatic shift in the ratio of Th1 : Th2 responses does not account for the resistance to disease. Resistance conferred by the lack of SOCS1 is specific since the related SOCS2, also implicated in Th1-mediated responses, did not seem to be involved in the development of disease. Understanding the mechanism by which SOCS1 deficiency protects mice from cerebral malaria may allow the manipulation of its activity and alleviate pathology.
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PMID:The lack of suppressor of cytokine signalling-1 (SOCS1) protects mice from the development of cerebral malaria caused by Plasmodium berghei ANKA. 1291 18

This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty-three children admitted to the hospital with cerebral (CM) and 10 children with non-cerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF-alpha) and transforming growth factor (TGF-beta1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF-beta1 and TNF-alpha decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF-alpha and TGF-beta1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF-beta and higher levels of TNF-alpha than those in lighter levels of coma. The serum TNF-alpha levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF-alpha and higher levels of TGF-beta than those with a longer duration of illness before admission. In conclusion, this study shows that TNF-alpha and TGF-beta1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF-alpha and TGF-beta levels were inversely related both in serum and CSF.
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PMID:Cerebral malaria in children: serum and cerebrospinal fluid TNF-alpha and TGF-beta levels and their relationship to clinical outcome. 1292 82

Plasmodium falciparum-infected erythrocytes often are sequestered in the placenta and stimulate the accumulation of maternal mononuclear cells. In this study, the role that chemokines and cytokines play in mediating the inflammatory response was investigated. Placental parasites elicited a statistically significant increase in the levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10, in plasma collected from the intervillous space. Explants of fetal tissue from malaria-positive placentas also secreted significantly enhanced amounts of IFN-gamma. Culture supernatant of maternal intervillous leukocytes obtained from infected placentas contained significantly higher levels of TNF-alpha, IL-10, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and IFN-gamma inducible protein-10 than did cultures of white blood cells obtained from uninfected placentas. Taken together, these results show that both fetal and maternal cells secrete inflammatory and immunoregulatory cytokines in response to P. falciparum and suggest that beta-chemokines produced by maternal cells contribute to the accumulation of macrophages in the intervillous space.
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PMID:Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. 1451 30

The choice of the host in studying host-parasite interactions is of crucial importance, and the use of a natural host is most appropriate in answering pertinent questions related to human malaria. The Grammomys surdaster is the natural host and reservoir of the rodent malaria parasite Plasmodium berghei. This natural host is difficult to protect by irradiated sporozoite immunization, a situation comparable to what has been observed in humans with P. falciparum. This is in contrast to the complete protection that can be induced in artificial hosts like inbred mice strains. The natural host is highly susceptible to P. berghei hepatic stage infections. Immunization with irradiated sporozoites in Grammomys generates blocked hepatic stage parasites and immunized Grammomys protected upon live sporozoite challenge generate antibody and T cell proliferative responses to these hepatic stages. Associated with proliferation, cytokines are secreted into culture supernatants constituted mainly of Interferon gamma, negligible amounts of TNF-alpha, and no IL-4. Natural host-parasite interactions of Grammomys surdaster-P. berghei can help define the effector mechanism(s) in the Plasmodium falciparum-human interaction.
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PMID:Rodent malaria in the natural host--irradiated sporozoites of Plasmodium berghei induce liver-stage specific immune responses in the natural host Grammomys surdaster and protect immunized Grammomys against P. berghei sporozoite challenge. 1451 35

Transforming growth factor-beta is an essential moderator of malaria-induced inflammation in mice. In this study, we show that the virulence of malaria infections is dependent upon the cellular source of TGF-beta and the timing of its production. C57BL/6 mice infected with a nonlethal (Py17X) strain of Plasmodium yoelii produce TGF-beta from 5 days postinfection; this correlates with resolution of parasitemia, down-regulation of TNF-alpha, and full recovery. In contrast, infection with the lethal strain Py17XL induces high levels of circulating TGF-beta within 24 h; this is associated with delayed and blunted IFN-gamma and TNF-alpha responses, failure to clear parasites, and 100% mortality. Neutralization of early TGF-beta in Py17XL infection leads to a compensatory increase in IL-10 production, while simultaneous neutralization of TGF-beta and IL-10R signaling leads to up-regulation of TNF-alpha and IFN-gamma, prolonged survival in all, and ultimate resolution of infection in 40% of Py17XL-infected animals. TGF-beta production can be induced in an Ag-specific manner from splenocytes of infected mice, and by cross-linking surface CTLA-4. CD25(+) and CD8(+) cells are the primary source of TGF-beta following Py17X stimulation of splenocytes, whereas Py17XL induces significant production of TGF-beta from adherent cells. In mice immunized against Py17XL, the early TGF-beta response is inhibited and is accompanied by significant up-regulation of IFN-gamma and TNF-alpha and rapid resolution of challenge infections.
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PMID:Differential induction of TGF-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. 1460 47

In areas of high malaria endemicity, women have increased susceptibility to malaria during pregnancy characterized by placental parasitemia. Our previous studies in children with malaria demonstrate that suppression of leukocyte-derived prostaglandin-E(2) (PGE(2)) is associated with enhanced pathogenesis. To examine the role of PGE(2) as an immunoregulatory molecule in placental malaria, PGE(2) was determined in cultured intervillous blood mononuclear cells (IVBMCs) from aparasitemic and parasitemic women. PGE(2) was significantly lower in parasitemic women at all gravidities. Women with a positive antenatal peripheral parasitemia who were negative for placental malaria (PM) at term produced the highest PGE(2) levels. Suppression of PGE(2) was associated with increasing amounts of hemozoin (malarial pigment) acquired during the natural infection. PGE(2) regulatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, were non-significantly increased in IVBMC containing an intermediate amount of hemozoin and significantly suppressed in IVBMC with high levels of hemozoin. Results presented here show that in vivo acquisition of high levels of hemozoin by IVBMC leads to decreased synthesis of PGE(2), IL-10, and TNF-alpha.
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PMID:In vivo acquisition of hemozoin by placental blood mononuclear cells suppresses PGE2, TNF-alpha, and IL-10. 1462 57


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