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

Reports linking human malarial illness and pathology with serum tumor necrosis factor (TNF) levels are now common, although the association is not always precise. Possible reasons for this discrepancy include the reported variation in levels of interleukin-1 (IL-1), a cytokine known to synergize with TNF. We have examined the extent of synergy between recombinant human TNF and either recombinant human IL-1 alpha or recombinant human IL-1 beta in producing hypoglycemia and increasing plasma levels of nitric oxide in malaria (Plasmodium vinckei)-infected CBA mice. Very low concentrations of either IL-1 alpha or IL-1 beta, with negligible effects on their own, greatly enhanced the effectiveness of TNF in bringing about these changes. In particular, synergy in generating nitric oxide, a mediator argued to induce cerebral malaria, was profound. Thus, variation in generation of IL-1 during infection provides one explanation for the poor correlation sometimes encountered between serum TNF levels and clinical condition.
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PMID:Tumor necrosis factor and interleukin-1 synergy in the context of malaria pathology. 802 67

Lactic acidosis and hypoglycemia are potentially lethal complications of falciparum malaria. We have evaluated the pharmacokinetics and pharmacodynamics of dichloroacetate ([DCA], 46 mg/kg infused over 30 minutes), a stimulant of pyruvate dehydrogenase and a potential treatment for lactic acidosis, in 13 patients with severe malaria and compared the physiological and metabolic responses with those of a control group of patients (n = 32) of equivalent disease severity. The mean +/- SD peak postinfusion level of DCA was 78 +/- 23 mg/L, the total apparent volume of distribution was 0.75 +/- 0.35 L/kg, and systemic clearance was 0.32 +/- 0.16 L/kg/h. Geometric mean (range) venous lactate concentrations in control and DCA recipients before treatment were 4.5 (2.1 to 19.5) and 5.5 (2 to 15.4) mmol/L, respectively (P > .1). A single DCA infusion decreased lactate concentrations from baseline by a mean of 27% after 2 hours, 40% after 4 hours, and 41% after 8 hours, compared with decreases of 5%, 6%, and 16%, respectively, in controls (P = .032). These changes were preceded by rapid and marked decreases in pyruvate concentrations. Arterial pH increased from 7.328 to 7.374 (n = 10, P < .02) 2 hours after the infusion. Hypoglycemia was prevented by infusing glucose at 3 mg/kg/min. There was no clinical, electrocardiographic, or laboratory evidence of toxicity. These results suggest that DCA should be investigated further as an adjunctive therapy for severe malaria.
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PMID:Dichloroacetate for lactic acidosis in severe malaria: a pharmacokinetic and pharmacodynamic assessment. 805 55

Groups of five dogs were vaccinated with Babesia canis antigens from in vitro culture in combination with saponin as adjuvant. Protection against challenge infection was evident as diminished clinical disease, decrease in parasitaemia, and a less marked fall in haematocrit values. Recovery from infection occurred at the time a memory immune response became effective (from Days 5 to 6 after challenge infection onwards). The effect was dose dependent, the highest antigen dose being most effective. A lysate of normal erythrocytes did not have protective activity, indicating that a parasite component was responsible for protection. Unlike the malaria situation, disease was not associated with elevated levels of tumour necrosis factor in the plasma, nor with hypoglycaemia. Disease appeared to be the result of the activity of a parasite product, which could have triggered reactions which led to sequestration of erythrocytes from the peripheral venous blood. As a result, the packed cell volume decreased, and organs such as lymph nodes and spleen became congested. As soon as immunity had developed there was a rapid increase in the peripheral erythrocyte number, and congestion of the spleen diminished, indicative of restored capillary blood flow. The results further suggest that vaccination with a soluble parasite product blocks the trigger of this pathological process.
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PMID:Vaccination of dogs against Babesia canis infection using antigens from culture supernatants with emphasis on clinical babesiosis. 807 6

Tumour necrosis factor-alpha (TNF-alpha) is an endogenous mediator of shock and inflammation. Many of the life-threatening and severe pathologies associated with complicated and cerebral malaria are thought to result from the overproduction of this cytokine in response to agents of parasite origin. The identification and characterization of these agents may therefore provide the molecular basis for a detailed understanding of the disease process. Recently it has been shown that glycosylphosphatidylinositols are a novel class of glycolipid toxin produced by the parasite, which substitute for the endogenous inositolglycan-based signal transduction pathways of the host. Glycosylphosphatidylinositol stimulates high levels of TNF-alpha and interleukin-1 production by macrophages and induces hypoglycaemia through an insulin-mimetic activity, and may therefore contribute to the cerebral syndrome and other malarial pathophysiology. That monoclonal antibodies to parasite-derived glycosylphosphatidylinositol can neutralize the toxic activities of whole parasite extracts is also demonstrated here. These findings suggest a central role for glycosylphosphatidylinositol of parasite origin in the aetiology of severe malaria and suggest novel approaches for the immunotherapy or immunoprophylaxis of disease.
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PMID:Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria. 812 25

Evaluation of 446 infants and young children (6 months to 5 years olds) with malaria parasitaemia showed a significant relationship (P < 0.05- < 0.001) (a) between coma and age, pattern of convulsions, haematocrit, and blood glucose, and (b) between the severity of parasitaemia and risk of convulsions, prevalence of hepatosplenomegaly, and severe anaemia. No significant relationship was observed between convulsions and temperature or haematocrit. Comatose children were older and had a higher prevalence of repeated convulsions, severe anaemia, and hypoglycaemia than non-comatose children. Convulsions, hepatosplenomegaly, and severe anaemia were more prevalent in children with moderate-severe parasitaemia. It is concluded that convulsions with malaria are more often a manifestation of cerebral dysfunction rather than being simply febrile in nature. All forms of cerebral dysfunction in malaria, including repeated convulsions, should be managed as being clinical manifestations of cerebral malaria.
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PMID:Convulsions with malaria: febrile or indicative of cerebral involvement? 813 57

Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous blood lactate concentrations were almost twice as high in fatal cases as in survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001). Treatment with quinine was associated with significantly more episodes of post-admission hypoglycaemia when compared with artemether or chloroquine. After treatment, lactate concentrations fell rapidly in survivors but fell only slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after admission) proved to be the best overall prognostic indicator of outcome in this series. Lactic acidosis is an important cause of death in severe malaria.
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PMID:Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance. 815 8

Computed tomography was performed on 14 unconscious Kenyan children recovering from cerebral malaria (seven of whom had another scan 12-120 days later) to elucidate the cause of intracranial hypertension and neurological sequelae. Brain swelling, defined as a loss of cerebrospinal fluid spaces, was documented in six children, while a further two had conspicuously small ventricles only. There was severe intracranial hypertension in the two children with definite brain swelling in whom intracranial pressure was monitored. There was no evidence of acute hydrocephalus or vasogenic oedema. Four children with brain swelling also had widespread low density areas suggestive of ischaemic damage. The patterns of damage were not uniform but were consistent with a critical reduction in cerebral perfusion pressure (which was documented in the two in whom this was monitored), hypoglycaemia, or status epilepticus. All four had serious neurological sequelae. These data suggest that brain injury in cerebral malaria may be due in part to secondary systemic and intracranial factors as well as to the direct effect of intravascular sequestration.
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PMID:Brain swelling and ischaemia in Kenyans with cerebral malaria. 818 59

Beginning in 1981, Prapokklao Regional Hospital in Chantaburi, Thailand, admitted all pregnant women with malaria to the obstetrics unit so midwives and obstetricians could learn how to better detect early signs or symptoms of malaria. Prior to 1981, they treated these women with quinine hydrochloride in a 500 ml 5% dextrose drip for 8 hours. They failed to detect hypoglycemia and pulmonary edema, however, resulting in many deaths. After 1981, they used 20 mg/kg quinine hydrochloride in a 250 ml 5% dextrose drip in 4 hours then 10 mg/kg quinine hydrochloride in a 250 ml 5% dextrose drip at the same rate at 8 hour intervals. Once the patient could take the drug orally, they administered 600 mg quinine sulfate at 8 hourly intervals for 7 days. They measured blood bilirubin levels and performed renal function tests on admission and on days 2 and 5. They monitored blood sugar levels on admission, at hourly intervals during intravenous quinine treatment, and every 4 hours during oral quinine treatment. Clinicians encouraged women who could drink to drink glucose syrup during quinine treatment. If, during treatment, a patient experienced unconsciousness or convulsions or blood sugar levels fell below 60 mg/dl, they would administer 100 ml of 50% glucose. If bilirubin levels remained high or a patient became jaundiced on day 2, clinicians monitored bilirubin on days 3 and 4. If levels increased, they reduced the dose 33% until the situation improved. They recorded urinary output hourly and measured central venous pressure. If the patient had normal pressure, but urinary output was less than 30 ml/hour, clinicians prescribed a diuretic. They kept patients in a propped-up position to reduced the likelihood of pulmonary edema. They monitored fluid intake and output and, in severe cases, central venous pressure. They allowed just enough fluid intake to maintain the pressure at 10-12 mm H20 and urine output at no less than 30 ml/hour. These efforts reduced maternal deaths in the unit from 341 to 54/100,000 live births (1981 - 8 deaths; 1986 - no deaths).
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PMID:Malaria in pregnant women: action for survival. 818 99

To investigate metabolic disturbances in an animal model of human malaria, four rhesus monkeys (Macaca mulatta) were infected with Plasmodium coatneyi, a parasite which induces cytoadherence of infected erythrocytes. When moribund or the parasitaemia had plateaued, the monkeys were sacrificed (3 animals) or treated with chloroquine (1 animal). Blood and cerebrospinal fluid (CSF) were sampled at intervals between inoculation and sacrifice or treatment. Arterial and CSF glucose and lactate rose during infection, indicating evolving insulin resistance. The arteriovenous difference in glucose concentration also increased, consistent with increased glucose consumption by parasitised tissues. Arterial plasma lactate rose but a positive arteriovenous concentration difference suggested tissue lactate uptake. The animal with the highest plasma lactate at sacrifice remained hyperglycaemic but also had the highest CSF lactate, the greatest cerebral sequestration and neurological depression, and biochemical and histological evidence of severe hepatic pathology. Serum cholesterol and corrected serum calcium fell consistently during infection; serum phosphate was also reduced in animals without renal impairment. These preliminary results indicate that lactic acidosis is a late complication of severe malaria and, by implication from this and other studies, hypoglycaemia occurs even later; other metabolic changes during P. coatneyi infection in rhesus monkeys also parallel those of severe falciparum malaria in humans. The model could be used in further studies of malaria-associated metabolic dysfunction and its management.
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PMID:Metabolic disturbances in Plasmodium coatneyi-infected rhesus monkeys. 802 92

1. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16-30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence. 2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P < 0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2m-units/l during quinine infusion (P < 0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mg min-1 kg-1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min-1 kg-1, n = 11] and correlated significantly with the admission parasitaemia (P < 0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (2.58-4.16) to 2.66 [1.94-3.94) mg min-1 kg-1] whereas clearance did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose turnover in pregnant women with acute malaria. 830 56


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