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

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.
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PMID:Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. 822 94

Granulocyte macrophage-colony stimulation factor (GM-CSF), which is a haematopoietic cytokine generated by activated T lymphocytes and macrophages during infection, was investigated for its effects on human neutrophil-mediated killing of asexual blood forms of Plasmodium falciparum. Pretreatment of neutrophils with human recombinant-GM-CSF markedly increased the parasite killing (measured by a radiometric assay), in the presence of normal serum (containing complement), immune serum (IS), purified IgG (from IS) or heat inactivated IS. GM-CSF pretreatment also enhanced phagocytosis of the parasite by neutrophils and the expression of CR3, Fc gamma RII and Fc gamma RIII receptors. Treatment of neutrophils with a combination of GM-CSF and TNF resulted in a synergistic increase in phagocytosis and killing of the parasite. The findings suggest that GM-CSF is likely to form part of the cytokine network responsible for regulating the antiparasitic activity of the neutrophil in malaria.
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PMID:GM-CSF-induced priming of human neutrophils for enhanced phagocytosis and killing of asexual blood stages of Plasmodium falciparum: synergistic effects of GM-CSF and TNF. 922 65

32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed unusual complications and/or manifestations are reported. The acute manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one. The other features were concomitant salmonellosis 2, meningitis 1, renal failure 3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia with tremors 3. Bone marrow in these cases was hypercullular with increase plasma cells. Liver biopsy revealed lymphocytic infiltration. There was no case with permanent neurogical deficit. All patients with pulmonary oedema and multiple organ dysfunction died but chronic syndrome patients recovered fully. Early recoginition of atypical manifestation and prompt treatment will decrease the mortality and morbidity due to malaria.
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PMID:Unusual acute and chronic complications of malaria. 928 1

We examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-6, granulocyte macrophage-colony stimulating factor (GM-CSF), and the anti-inflammatory cytokine IL-10, and their expression in kidneys acutely infected with murine malaria parasite P. berghei ANKA in C57BL/6J mice. Groups of six mice sacrificed on days 5, 10, 15, and 20, and normal controls were used for cytokine analysis. High concentrations of TNF-alpha and IL-10 were detected in plasma as shown by ELISA, and elevated levels of mRNA specific for TNF-alpha and IL-10 in infected kidneys were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with antibodies against TNF-alpha, IL-1 alpha, IL-6, GM-CSF and IL-10 for immunohistochemistry showed markedly enhanced staining for TNF-alpha, and progressively increased staining for IL-1 alpha and IL-6 both in the tubules and the walls of arteries during the course of infection. The endothelia of blood vessels and inflammatory cells located around small arteries showed positive staining for GM-CSF from day 10 onwards. Unlike the staining for proinflammatory cytokines, the anti-inflammatory cytokine IL-10 showed strongly positive staining in normal tubules and walls of arteries, especially in the brush border of proximal tubules, but the staining intensity decreased dramatically after day 15 post-infection. A strongly positive correlation was found between the antibody staining for TNF-alpha/IL-1 alpha in tubules, and the severity of proteinuria. In contrast, there was an inverse correlation between the staining for IL-10 with TNF-alpha/IL-1 alpha, and the degree of proteinuria. Plenty of pigmented macrophages showed positive staining both for proinflammatory and anti-inflammatory cytokines in the tubulointerstitium. Our findings imply that the up-regulation of proinflammatory cytokines and the dysregulation of anti-inflammatory cytokines are involved in the pathogenesis of tubulointerstitial nephritis associated with malaria.
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PMID:Dysregulation of cytokine expression in tubulointerstitial nephritis associated with murine malaria. 955 90

Mefloquine represents a promising antimalarial drug against Plasmodium falciparum. It has been related to an increase in seizure frequency in epileptic patients and should not be administered to patients with a history of convulsions, epilepsy in first degree relatives, or serious psychiatric disorders. We report a case of a man from the Ivory Coast complaining of fever, headache and anemia treated with chloroquine and subsequently with mefloquine in the suspicion of malaria, even in the absence of laboratory confirmation. When the patient came to our division, malaria was excluded, but the patient developed two convulsive episodes, respectively 4 and 7 days after the ingestion of the second therapeutic dose of mefloquine. Further investigation was performed; particularly an EEG showed abnormalities compatible with tendency for seizures, diffuse waves and spikes. CSF culture was positive for M. tuberculosis as well as urine, sputum and blood cultures. Anti-HIV antibodies were positive, so the final diagnosis was tuberculosis in HIV infection. As seizures are common signs of cerebral tuberculomas, but not of meningitis it is possible that tubercular meningitis might have enhanced severe neuropsychiatric side effects of mefloquine. Physicians should be aware that treatment with mefloquine with concomitant meningitis could have a risk of development of grand mal seizure.
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PMID:Mefloquine-induced grand mal seizure in tubercular meningitis. 997 35

Malaria infections often cause glomerulonephritis (GN), and multiple factors have been implicated in the pathogenesis of glomerular injury. The role of cytokines in malaria associated glomerulonephritis has not been clearly defined. To study the importance of cytokines in malarial nephritis, we investigated the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6, IL-10 and granulocyte macrophage-colony stimulating factor (GM-CSF) in kidneys acutely infected with murine malaria parasite Plasmodium berghei ANKA in C57BL/6 J mice. Groups of six mice sacrificed on days 5, 8-10, 15, and 20 postinfection, and normal controls were used for cytokine analysis. Elevated levels of messenger RNA (mRNA) specific for these cytokines in infected kidneys after day 5 postinfection were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with specific antibodies against TNF-alpha, IL-1alpha, IL-6, IL-10 and GM-CSF by immunohistochemistry showed that the staining for these cytokines on the glomeruli was positive from day 10 postinfection, and increased progressively, mainly in the infiltrating macrophages and the glomerular mesangium. Strong correlation was found between the expression of TNF-alpha with IL-6, and IL-1alpha with IL-6. The expression of TNF-alpha, IL-1alpha, IL-6, and IL-10 also strongly correlated with the severity of proteinuria. Our findings show that there is up-regulation of cytokines in the pathogenesis of glomerulonephritis associated with murine malaria infection.
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PMID:Up-regulation of cytokines in glomerulonephritis associated with murine malaria infection. 1046 63

Of 51 consecutive children with cerebral malaria, fever, convulsions, and drowsiness were the commonest presenting symptoms. Decerebrate and decorticate postures and absent cornea reflex were the commonest brain stem signs. Opening lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia occurred in 17 (33%). Acute renal failure was not uncommon; the combination of hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred. Disturbances of acid-base status were present in all 40 children in whom it was assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the present measures aimed at reducing morbidity and morality in children with cerebral malaria, efforts should be directed at rapid assessment of renal function and prompt correction of such dysfunction if found.
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PMID:Clinical study of cerebral malaria in African children. 1089 20

Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.
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PMID:Evaluation of CSF-adenosine deaminase activity in tubercular meningitis. 1099 88

Nitrate levels in CSF and sera from 16 coma and 19 noncoma falciparum malaria patients were determined using nitric oxide colorometric assay. The medians (range lower, upper limits) of nitrate in sera of comatose and noncomatose patients were 0.28 (0.11, 1.24) and 0.23 (0.05, 0.87) microM, respectively. The medians of nitrate level in CSF of coma and noncoma cases were 0.09 (0.01, 0.28) and 0.15 (0, 1.18) microM, respectively. There was no difference of nitrate level in sera and CSF from comatose or noncomatose patients compared to that in normal sera and CSF. The amount of nitrate in sera and CSF of both groups was not significantly correlated with coma depth, parasitemia, parasite clearance time and time to recovery. Contrast to our in vitro study using immunoperoxidase staining, we found inducible nitric oside synthase production by brain endothelial cells during 4-24 hours of coculturing with late stage of P. falciparum infected red blood cells. These results suggests that malaria severity can not be differentiated by nitrate level in body fluid.
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PMID:Lack of association between CSF nitrate and sera nitrate in falciparum malaria infection. 1155 75

The protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and synthetic peptide met-enkephalin (M-ENK) against blood-induced Plasmodium berghei infection in Swiss mice was investigated. Mice co-administered with rmGM-CSF (10.0 mug/kg) and M-ENK (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete elimination) of parasitaemia compared to vehicle-treated controls. However, when administered separately, neither of these agents induced any detectable protective effect. Surprisingly, mice similarly co-administered with rmGM-CSF (10.0 mug/kg) and higher doses of M-ENK (10.0 mg/kg), showed no protection. Polyclonal neutralizing (100%) antibody to rmGM-CSF abrogated the combined protective effect of these agents. Additionally, naloxone (10.0 mg/kg/day x 6, i.p.), a non-selective, opioid receptor antagonist, also blocked the combined protection. Mice that survived the challenge showed a significant increase (p < 0.05) in total circulating leukocytes counts, and the pool-size and the phagocytic activity of both the peritoneal and splenic macrophages, ex vivo. Silica (3.0 mg/mouse, i.v.) abrogated the combined protective effect of rmGM-CSF and M-ENK. These results indicate that co-administration of rmGM-CSF and dose dependent quantities of M-ENK in P. berghei-infected mice can protect against malaria, apparently through macrophage-mediated mechanisms.
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PMID:Protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin. 1156 34


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