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

Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of oxygen transport, have been previously found during Plasmodium vivax infections and in acidotic infants. We measured methaemoglobin in the following 5 groups of children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50), including 32 with complete recovery (CMCR) and 18 with death or neurological sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin levels were elevated in all groups with malaria, forming up to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated with disease severity and severity of anaemia. Mean methaemoglobin levels in children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8% respectively; the mean levels in those with clinical disease were significantly higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS, respectively. In the presence of parasite sequestration, impaired tissue perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a further reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a minority of anaemic and acidotic patients with severe falciparum malaria.
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PMID:Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria. 876 75

Cell-cell interactions are important in intravascular inflammation. Neutrophils and monocytes adhere to the vascular endothelium and release mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and reactive oxygen species. Red blood cells (RBC) from patients with malaria, sickle cell anemia, and diabetes also adhere to endothelial cells. The objectives of this investigation were to develop a bovine system of RBC adhesion to endothelial cells and to begin to investigate the mechanisms involved in the RBC adhesion. We show that 51Cr-RBC adhere to bovine pulmonary artery endothelial cells (BPAEC) after stimulation of both cell types with endotoxin (ETX; 50 micrograms/ml). RBC adhesion to BPAEC depended on the ETX concentration and the presence of divalent cations. TNF-alpha, IL-1 beta, and antioxidants (superoxide dismutase; catalase; and dimethyl sulfoxide) all induced RBC adhesion to BPAEC. Phosphatidylserine, which has been implicated in adhesion of sickle cells and aged RBC to endothelium, reduced RBC adhesion to BPAEC, whether ETX-treated or not. In conclusion, ETX, proinflammatory cytokines and, surprisingly, antioxidants increase RBC adherence to BPAEC monolayers. RBC adhesion to endothelium is decreased by phosphatidylserine.
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PMID:Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells. 877 24

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice. After artemether or chloroquine treatment, the ROI production was significantly enhanced. The interferon-gamma induced production of reactive nitrogen intermediates (RNI) was slightly elevated in mice with cerebral malaria, but markedly elevated in artemether or chloroquine treated mice when compared with naive mice. Moreover, high levels of inducible nitric oxide synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or chloroquine. These findings suggest that increased production of ROI and RNI after chemotherapy may play a protective role for the host during malaria.
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PMID:Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether. 885 61

Malaria affects world-wide more than 200 million people, of which 1-2 million die every year. New drugs and treatment strategies are needed to face the rapidly increasing problems of drug resistance. During a malaria infection, both host and parasite are under oxidative stress. Increased production levels of reactive oxygen species (ROS, e.g superoxide anion and the hydroxyl radical) are produced by activated neutrophils in the host and during degradation of haemoglobin in the parasite. The effects of ROS in malaria can be both beneficial and pathological, depending on the amount and place of production. Enhanced ROS production after the administration of pro-oxidants, which is directed against the intra-erythrocytic parasite, inhibits the infection both in vitro and in vivo. However, ROS are also involved in pathological changes in host tissue like damage of the vascular endothelial lining during a malaria infection (cerebral malaria). Pro-oxidants support the host defense against the parasite when working in or near the infected cell but potentially cause vascular damage when working on or near the vascular lining. Examples of pro-oxidants are found among xenobiotics and food components. Important new drugs belonging to the class of pro-oxidants are artemisinin and its derivatives. Anti-oxidants potentially counteract these agents. Treatment with anti-oxidants or chelators of metals to prevent their catalytic function in the generation of ROS may prevent vascular pathology. In addition, the iron chelator desferrioxamine, exhibits an antiparasitic activity, because iron is also essential for the proliferation of the parasite. Cytokines play an important role in ROS-related pathology of malaria, though their mechanism of action is not completely elucidated. This field might bring up new treatment concepts and drugs. Drugs which prevent host pathology, such as the cerebral complications might be life saving.
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PMID:Oxidative stress in malaria; implications for prevention and therapy. 887 27

Data collected from 200 children admitted to a hospital on the Kenyan coast who met a broad definition of severe acute respiratory infection (ARI) indicated that simple clinical signs alone are unable absolutely to distinguish severe ARI and severe malaria. However, laboratory data showed that marked differences exist in the pathophysiology of unequivocal malaria and unequivocal ARI. Children in the former group had a higher mean oxygen saturation (97 vs. 94, P < 0.001), mean blood urea level (5.3 vs. 1.9 mmol/L, P < 0.001) and geometric mean lactate level (4.5 vs. 2.1 mmol/L, P < 0.001), and lower mean haemoglobin level (5.3 vs. 9.0 g/dL, P < 0.001) and base excess (-9.4 vs. -2.6, P < 0.001) than those in the latter group. Using these discriminatory variables it was estimated that up to 45% of children admitted with respiratory signs indicative of severe ARI probably had malaria as the primary diagnosis. Radiological examination supported this conclusion, indicating that pneumonia characterized by consolidation was uncommon in children with respiratory signs and a high malarial parasitaemia (> or = 10,000/microliters). There is no specific radiological sign of severe malaria. In practice, all children with respiratory signs warranting hospital admission in a malaria endemic area should be treated for both malaria and ARI unless blood film examination excludes malaria. In those with malaria and clinical evidence of acidosis, but no crackles, antibodies may be withheld while appropriate treatment for dehydration and anaemia is given. However, if clinical improvement is not rapid, antibiotics should be started.
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PMID:Clinical overlap between malaria and severe pneumonia in Africa children in hospital. 901 8

This study investigates the effect of orally administered testosterone on serum testosterone levels and immune responses including outcome of Plasmodium chabaudi malaria. Female C57BL/10 mice were fed on a diet impregnated with 17 alpha-methyl-testosterone for 3 weeks. This raised the circulating testosterone levels from 0.28 ng/ml to 2.69 ng/ml on the average. In these mice, blood-stage infections of P. chabaudi resulted in a lethal outcome, whereas protective immunity developed in about 80% of mice fed on control diet without testosterone. Dietary 17 alpha-methyl-testosterone reduced the capacity of peritoneal cells to generate reactive oxygen intermediates after stimulation with C3b-coated zymosan and phorbol-myristate-acetate. Also, mice fed on dietary 17 alpha-methyl-testosterone responded to heat-killed Salmonella typhimurium with a higher increase in serum TNF, whereas the induced increase in the production of IL-10 by spleen cells was largely suppressed and no effect was found with respect to the production of IFN-gamma and IL-4. Our data indicate that the method of oral administration of 17 alpha-methyl-testosterone raises circulating testosterone to levels that impair protective immune responses to P. chabaudi malaria.
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PMID:Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malaria. 907 23

Morbidity and mortality due to malaria remains an important health problem for travelers visiting endemic zones. In this population, typical episodes of chills and fever followed by diaphoresis are not always observed; inaugural signs may limited to low-grade fever accompanying digestive disorders. Early diagnosis is nevertheless essential to prevent progression to acute pernicious malaria. Blood smears, quantitative butty coat (QBC) test or the Parasight test can give rapid diagnosis. Chloroquine is the drug of choice for Plasmodium vivax, P. ovale or P. Malariae infection, but chloroquine-resistant P. falciparum is widespread in tropical zones and resistant P. vivax has been reported in Indonesia. Currently, halofantrine is the best treatment for P. falciparum infection, although cardiac toxicity may occur in patients with a long QT on the electrocardiogram. Mefloquine can be alternative. The sulfadoxine-pyrimethamine combination is also used in many tropical zones because of its low cost and availability, but many resistant strains of P. falciparum have been identified. Use of quinine is also widespread in tropical zones. This basic antimalarial is rapidly effective but is also rapidly eliminated, necessitating repeated oral doses. Intramuscular injection may provoke necrosis. The main indication for quinine is acute pernicious P. falciparum malaria, but the drug is also used for simple episodes of fever in many tropical zones. Symptomatic care including fluid replacement, oxygen, transfusion, diuretics, respiratory assistance and dialysis may also be required in some cases. Use of corticosteroids or exsanguinotransfusion remains a question of debate. When administered rapidly, fever should regress within a few days. Neurological sequellae are exceptional after acute pernicious malaria in adults but may occur approximately 5% of children, emphasizing the importance of associating chemoprophylaxis and protection against insect bites. There has been much publicity concerning a vaccine, but results to date have been disappointing.
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PMID:[Malaria: what treatment today?]. 909 64

Adult respiratory distress syndrome (ARDS) has been a well recognized severe form of acute respiratory failure of multiple causes, which is characterized by intractable hypoxemia and an extremely high mortality rate. Forty-six cases of ARDS admitted to the Department of Medicine, Ramathibodi Hospital during a 39 months period were studied prospectively to explore the etiologic risk, positive end-expiratory pressure (PEEP) profiles, complications and outcome of treatment. There were 19 females and 27 males with the mean age of 40 years. Risks of ARDS included intra- and extra-pulmonary disease conditions and also tropical diseases such as malaria and leptospirosis. At the time of diagnosis, patients in this group were extremely hypoxic with a mean arterial/alveolar oxygen tension (PaO2/PAO2) of 0.125 +/- 0.04. After the application of appropriate PEEP, the mean PaO2/PAO2 ratios increased significantly in both survivor and non-survivor groups (0.277 and 0.199). The levels of PEEP used were below 16 and 11 cmH2O in 93.46% and 67.38% of cases, respectively. Complications of PEEP which included barotrauma and hypotension were found in 11 cases (23.9%) with a very high mortality rate (81.8%). There were 28 deaths of patients in this study, giving an overall 60.8% group mortality rate. Despite the similarities in most clinical profiles, the survivors, when compared to the non-survivors, showed a greater extent of improved oxygenation in response to the application of PEEP, with fewer PEEP complications. The present study would, hopefully, provide the Thai clinicians with valuable informations in the management of ARDS.
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PMID:Adult respiratory distress syndrome in Thai medical patients. 913 93

Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in Nigeria. On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial Plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria.
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PMID:Impaired microcirculation and tissue oxygenation in human cerebral malaria: a single photon emission computed tomography and near-infrared spectroscopy study. 923 Jul 83

Although paracetamol is routinely used to control fever in African children with Plasmodium falciparum, the usefulness of this treatment has not been established. In a randomized clinical trial, 50 children 2-7 years of age from Lambarene, Gabon, with P. falciparum malaria were treated with intravenous quinine and received either mechanical antipyresis alone (electric fanning, tepid sponging, and cool blankets) or in combination with paracetamol. The mean fever clearance time was 32 hours for children treated with paracetamol and 43 hours for those who received antipyresis alone--a nonsignificant difference. Parasite clearance time was significantly prolonged (by an average of 16 hours) in children who received paracetamol. Although plasma concentrations of tumor necrosis factor and interleukin-6 were similar in both groups, induced concentrations of tumor necrosis factor and the production of oxygen radicals were significantly lower in paracetamol-treated children. Overall, these findings indicate that paracetamol confers no benefits over mechanical antipyresis alone and actually prolongs parasite clearance time. Further studies are required, however, before recommendations for ancillary treatment can be changed.
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PMID:Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. 941 85


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