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Query: UMLS:C0024530 (malaria)
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Pentoxifylline, an inhibitor of tumor necrosis factor, was evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria admitted to the Bangkok (Thailand) Hospital for Tropical Diseases, in a 5-month period in 1994. All patients had 1 or more clinical manifestations of severe malaria, including cerebral malaria (n = 18), renal failure requiring dialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). Patients were randomly assigned to receive treatment for 72 hours with a combination of intravenously administered artesunate and either placebo (n = 15), low-dose (0.83 mg/kg/hour) pentoxifylline (n = 15), or high-dose (1.67 mg/kg/hour) pentoxifylline (n = 15). Overall severity was comparable in all 3 groups. Concentrations of tumor necrosis factor were reduced in all 3 groups 48 hours after treatment. There were no significant differences between groups in terms of parasite and fever clearance time, recovery time from coma in patients with cerebral malaria, duration of intubation in patients with respiratory distress, number of hemodialysis treatments required for patients with acute renal failure, or number of units of blood administered to patients in need of transfusion. These findings suggest that the addition of pentoxifylline to artesunate therapy for severe malaria produces no evident clinical benefit.
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PMID:Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand. 954 17

Acute renal failure, disseminated intravascular coagulation, ARDS, hypoglycaemia, coma or epileptic seizures are manifestations of severe Plasmodium falciparum malaria. On the other hand, vivax malaria or benign tertian malaria is usually free from complications. In the present report we describe a case of acute tertian malaria with a severe and complicated course. In this situation bacterial coinfection should always be suspected and treated empirically with broad-spectrum antibiotics, until the results of cultures are available. Mixed plasmodial infection (P. vivax and P. falciparum) must be excluded by repeated and meticulous examination of blood smears. Newer techniques such as PCR processing or ParaSight F Test are mentioned.
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PMID:[ARDS in plasmodium vivax malaria]. 969 37

Renal and renal-related disorders commonly occur in infection with Plasmodium falciparum, which can cause fluid and electrolyte disorders, glomerulonephritis, and acute renal failure (ARF). It appears that ARF and other life-threatening complications in falciparum malaria are not directly caused by the parasite itself but are the result of interaction of mechanical, immunologic, and humoral components. P. falciparum-infected erythrocytes impair microcirculation and cause hemolysis. Glycosylphosphatidylinositol moieties covalently linked to the surface antigens of falciparum malarial parasites appear to act like endotoxin. Glycosylphosphatidylinositol, via CD14, which is a receptor on monocytes, stimulates monocytes to release tumor necrosis factor, which in turn enhances synthesis of various cytokine cascades and mediators. Besides contributing to ARF, these mediators also cause changes in blood volume status. The degree of vasodilatation caused by vasodilating mediators varies with the severity of infection. Increased vascular permeability by the mediators occurs in severe infection, which results in hypovolemia and contributes to ARF. Although the cornerstone of treatment of malaria still is antimalarial drugs, several new modalities of treatment targeting toxin, signal transduction, mediators, and cytokines have great potential.
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PMID:Falciparum malaria and the kidney: a model of inflammation. 974 Jan 51

Six patients with severe and complicated falciparum malaria (6.7 +/- 2.7 WHO criteria) were admitted to our Intensive Care Unit. All patients acquired the disease while travelling in tropical Africa without appropriate chemoprophylaxis. The clinical manifestations included hyperpyrexia (all patients), chills (4), sweating (2), asthenia (3), anorexia (2), headache (1), arthralgias (1), vomiting (4), diarrhoea or abdominal discomfort (3), jaundice (2) and disturbances of consciousness (4). All patients had anemia, thrombocytopenia, hyponatremia, hypoproteinemia, hypoalbuminemia, hypocalcemia and acute renal failure, in one case associated with anuria. A low grade parasitemia was observed in two patients and a high grade parasitemia (20%-58% of erythrocytes) in four. Exchange transfusion was performed only in high parasitemic patients and all of them survived. All patients were treated with quinine, a sulfonamide and pyrimethamine. Additionally, five patients received oxytetracycline, doxycycline or clindamycin. Three patients required hemodyalisis. Five patients had delirium, coma or seizures. All patients had at least one sign of hepatic impairment: liver enlargement, jaundice or increased bilirubin or aminotransferase levels. Two patients had spleen enlargement. Laboratory findings suggested disseminated intravascular coagulation in four patients. Four patients developed pulmonary changes and three of them required mechanical ventilation. A Swan-Ganz catheter was placed in four patients. In three of them (two with pulmonary edema) the pulmonary capillary wedge pressure was initially increased, which suggested a cardiogenic or hypervolemia mechanism, but soon returned to normal level. One patient with low grade parasitemia died because of adult respiratory distress syndrome after 18 days. In our series, the degree of parasitemia was not related to the severity of the disease.
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PMID:[Severe and complicated malaria. Report of six cases]. 977 80

Falciparum malaria remains a major killer in developing countries, particularly for African children. The sequestration of parasitized erythrocytes in the deep microvasculature is mostly mediated by their cytoadherence to activated endothelium. Proinflammatory cytokines and particularly tumor necrosis factor contribute to severe disease but the pathophysiology of coma remains poorly understood. In young children, features of severe malaria include severe anemia, hypoglycemia and cerebral malaria. Half of the children with neurological impairment actually have raised intracranial pressure, and seizures are extremely common. Clinical respiratory distress usually reflects severe lactic acidosis. In non immune adults, pictures of severe sepsis with shock, acute renal failure and respiratory distress syndrome are common and often associated with bacterial coinfection. Although chemotherapy of malaria is challenged by the continuing evolution of antimalarial resistance, quinine remains the first-line drug for severe disease. The optimization of symptomatic management of severe malaria remains a major concern in developing countries.
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PMID:[Severe malaria]. 978 Oct 74

Incidence of falciparum malaria in developed countries has increased in recent years due to tourism to tropical countries and immigration from Asia and Africa. In Switzerland, about 250 cases of malaria were reported in 1994 to the Federal Office of Health, including three cases with fatal outcome.1 The most commonly described complications of plasmodia infection are cerebral malaria, acute renal failure, and severe anemia with disseminated intravascular coagulation. However, pulmonary involvement occurs in 3 to 10% of cases and represents the most serious complication of this infection, with a lethality of 70%.2,3 Furthermore, a pronounced general immunosuppression has been reported in malaria patients, which may predispose them to opportunistic infections.4 We report a case of Plasmodium falciparum infection complicated by severe acute respiratory distress syndrome (ARDS) with development of systemic cytomegalovirus (CMV) infection leading to death. This evolution implies a severe immune deficiency associated with malaria, as previously suggested in the literature.
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PMID:Septic Shock due to Cytomegalovirus Infection in Acute Respiratory Distress Syndrome after Falciparum Malaria. 981 2

We studied 112 patients with malarial acute renal failure (ARF) during the period 1991-1997 at Bangkok Hospital for Tropical Diseases (Mahidol University, Bangkok, Thailand). Hemodialysis was performed in 101 (90.2%) of these patients. The mean number of times the patients were hemodialyzed was 6.5 (range = 1-27). Ninety-three (83.0%) patients were oliguric and the remainder were nonoliguric. Patients who had oliguric renal failure required more hemodialyses and had more complications than the nonoliguric patients. The oliguric patients had an eight-fold higher risk of requiring six or more hemodialyses (95% confidence interval = 1.2-53.9, P = 0.0008). The overall mortality rate was 10.7% (12 of 112). Eleven of the patients who died were jaundiced and eight of them had cerebral malaria with a Glasgow Coma Score < or = 8. We conclude that hemodialysis is a useful treatment for oliguric and nonoliguric ARF from severe malaria, particularly when initiated early in the course of the illness.
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PMID:Treatment of malarial acute renal failure by hemodialysis. 1007 41

A 53-year-old patient, after return from a short visit to the Ivory Coast, was admitted for suspicion of hepatic encephalopathy. An acute pernicious malaria was diagnosed with associating altered consciousness, hyperthermia, icterus, hepatomegaly, and oliguria. Blood tests showed acute renal failure, pancytopenia, disseminated intravascular coagulation, metabolic acidosis and parasitaemia at 12%. An intravenous therapy with quinine and doxycycline was started without delay. One day later, an exchange blood transfusion including a erythrapheresis and plasmapheresis was undertaken. The patient's general condition improved, and he was discharged from the ICU 22 days later. The indications for exchange blood transfusion in acute pernicious malaria are discussed.
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PMID:[Acute pernicious malaria treated with exchange transfusion]. 1042 88

Pulmonary edema is a serious complication of falciparum malaria that usually occurs in association with cerebral malaria, acute renal failure, high parasitemias, or delayed antimalarial treatment. From 1993 to 1996, 120 adult patients admitted to the intensive care unit of the Bangkok Hospital for Tropical Diseases were enrolled in a prospective study to assess the combination of artesunate and mefloquine for the treatment of cerebral malaria. Twenty-five patients (21%) presented with pulmonary edema and a majority developed complications in other organs as well, especially acute renal failure. In most patients (19 of 25), pulmonary edema was noted on the first day of admission and was associated with higher parasitemias and levels of acidemia, than in patients without pulmonary edema. Ten of the 25 patients diagnosed with pulmonary edema developed signs consistent with adult respiratory distress syndrome (ARDS). The mean central venous pressure when pulmonary edema was diagnosed was markedly lower in ARDS than in non-ARDS patients, supporting the argument that fluid imbalance is not essential for malaria-induced lung injury. Seven of 10 patients with ARDS died, 5 within 24 hours of admission, but there were no deaths in the 15 pulmonary edema patients without ARDS. Early diagnosis and prompt treatment remain important principles to reduce the morbidity and mortality associated with complicated falciparum malaria. This report emphasizes that ARDS, when concurrently occurs, is a poor prognostic clinical indicator in cerebral malaria.
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PMID:Pulmonary edema in cerebral malaria patients in Thailand. 1043 53

Pro- and antiinflammatory cytokines were measured on admission in 287 consecutive Vietnamese adults with severe falciparum malaria. Plasma interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations and the IL-6: IL-10 ratio were significantly higher in patients who died than in survivors (P<.001). On multivariate analysis, hyperparasitemia, jaundice, and shock were all associated independently with raised IL-6, IL-10, and interferon-gamma, and acute renal failure specifically with raised TNF-alpha levels. Cerebral malaria patients, particularly those without other vital organ dysfunction, had significantly lower levels of these cytokines (P=.006), reflecting a more localized pathology. Serial IL-6 and IL-10 measurements made on 43 patients who died and matched survivors indicated a relative deficiency in IL-10 production as death approached. Elevated plasma cytokines in severe malaria are associated with systemic pathologic abnormalities, not cerebral involvement. Both the overall magnitude of the cytokine responses and the eventual imbalance between the pro- and antiinflammatory responses are important determinants of mortality.
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PMID:The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. 1047 60


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