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)

The symptoms of severe malaria and their contribution to mortality were assessed in 290 children in northern Ghana. Common symptoms were severe anemia (55%), prostration (33%), respiratory distress (23%), convulsions (20%), and impaired consciousness (19%). Age influenced this pattern. The fatality rate was 11.2%. In multivariate analysis, circulatory collapse, impaired consciousness, hypoglycemia, and malnutrition independently predicted death. Children with severe malaria by the current World Health Organization (WHO) classification, but not by the previous one (1990), showed relatively mild clinical manifestations and a low case fatality rate (3.2%). In hospitalized children with severe malaria in northern Ghana, severe anemia is the leading manifestation, but itself does not contribute to mortality. In this region, malnutrition and circulatory collapse were important predictors of fatal malaria. The current WHO criteria serve well in identifying life-threatening disease, but also include rather mild cases that may complicate the allocation of immediate care in settings with limited resources.
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PMID:Manifestation and outcome of severe malaria in children in northern Ghana. 1530 5

The purpose of this prospective study conducted from March to December 2000 in the Internal Medicine Department of the Sanou Souro University Hospital in Bobo-Dioulasso, Burkina Faso was to evaluate the epidemiological, clinical, biological and prognostic features of severe malaria in adult patients according to their HIV status. During the study period HIV testing was performed in 37 of the 72 adults with confirmed severe malaria. Findings were positive in 12 cases and negative in 25. The mean age of the 12 seropositive patients with severe malaria was 32.4 +/- 2.8 years and most (50%) had used self-prescribed antimalarial treatment. The most common reasons for seeking medical care were fever, headache and deterioration of general health. The main manifestations of severe malaria were coma (n=4), generalized seizure (n=4) and circulatory collapse (n=4). Six patients (50%) presented two severe manifestations. Mean parasitemia at the time of admission was 4066 parasites/microl for seropositive subjects versus 8563 parasites/microl for seronegative subjects. Outcome of malaria included 4 deaths and 8 recoveries in the seropositive group versus 2 deaths and 23 recoveries in the seronegative group. Comparison with the group of 25 seronegative patients presenting severe malaria demonstrated no significant difference in mean age (p=0.96), self-prescribed antimalarial treatment (p=0.50), parasitemia upon admission (p=0.28), or mortality (p=0.07). However co-infected patients were found to have a higher incidence of anemia (P=0.01) and never presented certain manifestations of severe malaria. Further studies of co-infection by HIV infection and malaria (especially severe malaria) is needed given the high human and economic impact of these two diseases in sub-Saharan Africa.
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PMID:[Severe malaria and HIV in adult patients in Bobo-Dioulasso, Burkina Faso]. 1561 84

The population of Gulu District (northern Uganda) has been severely incapacitated by war, epidemics and social disruption. This study is aimed at describing disease patterns and trends in this area through a retrospective analysis of discharge records for 155205 in-patients of Lacor Hospital in the period 1992-2002. The burden of infectious diseases in childhood is overwhelming, with malaria accounting for the steepest increase in admissions. Admissions for war-related injuries and malnutrition fluctuated with the intensity of the war and the severity of famine. Emerging and re-emerging infections, such as HIV/AIDS, tuberculosis and Ebola, accounted for a heavy disease burden; however, there has been a trend for admissions related to HIV/AIDS and tuberculosis to decrease since the implementation of community-based services. Vulnerable groups (infants, children and women) accounted for 79.8% of admissions. Long-term war, population displacement, the collapse of social structures and the breakdown of the health system place people at a much greater risk of persistent, emerging and re-emerging infectious diseases, malnutrition and war-related injuries, shaping the 'disease profile of poverty'. Most of the disease burden results from infectious diseases of childhood, whose occurrence could be dramatically reduced by low-cost and effective preventive and curative interventions.
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PMID:The disease profile of poverty: morbidity and mortality in northern Uganda in the context of war, population displacement and HIV/AIDS. 1565 26

We report 11 cases of severe Plasmodium vivax malaria in Bikaner (western India). Patients exhibited cerebral malaria, renal failure, circulatory collapse, severe anemia, hemoglobinurea, abnormal bleeding, acute respiratory distress syndrome, and jaundice. Peripheral blood microscopy, parasite antigen-based assays, and parasite 18s rRNA gene-based polymerase chain reaction showed the presence of P. vivax and absence of P. falciparum.
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PMID:Plasmodium vivax malaria. 1570 38

From the 1950s until 1979 malaria control in Afghanistan was implemented through a vertical programme managed by the government, but little of the original programme remained functional by the early 1990s. Delivery of basic health care including malaria diagnosis and treatment was done by non-governmental organisations (NGOs) and UN agencies, which organised cross-border operations from Pakistan and Iran and placed much less emphasis on vertical programming. From 1992 the situation in the east of Afghanistan became stable enough to allow the establishment of a network of NGO-supported clinics and to introduce standardised training and monitoring of microscopists and clinical staff, coordinated by a lead agency specialising in malaria. After the collapse of the Taliban in 2001 and the subsequent establishment of an interim government, the first steps in health-system rehabilitation have been taken. The gradual integration of malaria control into routine health-care delivery is planned. This process should be guided by the knowledge and experience gained during the complex emergency and a focus on malaria should be maintained until the disease is brought under control.
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PMID:Malaria control in Afghanistan: progress and challenges. 1596 40

The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.
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PMID:Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. 1609 85

Plasmodium falciparum serine repeat antigen (SERA5) is a promising asexual blood stage malaria candidate vaccine. However, there is a paucity of information about natural immune responses to SERA5 in children from malaria-endemic regions. We undertook a hospital-based case-control study of severe malaria in Apac District, Northern Uganda, in children 6-59 months of age. The commonest symptoms observed in children with severe malaria (SM) were respiratory distress (53.4%) and prostration (40.4%) followed by circulatory collapse (7.4%), severe anemia (Hb < 5 g/dL, 7.0%), and seizures (2.6%). None of the SM children had impaired consciousness, coma, or cerebral malaria. We measured serum IgG antibodies using a recombinant construct of SERA5 (SE36) in enzyme-linked immunosorbent assays. High titers of IgG anti-SE36 were associated with protection against severe malaria in children under 5 years old.
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PMID:High titers of IgG antibodies against Plasmodium falciparum serine repeat antigen 5 (SERA5) are associated with protection against severe malaria in Ugandan children. 1647 69

This study reports on the first characterization of the alternative NADH:dehydrogenase (also known as alternative complex I or type II NADH:dehydrogenase) of the human malaria parasite Plasmodium falciparum, known as PfNDH2. PfNDH2 was shown to actively oxidize NADH in the presence of quinone electron acceptors CoQ(1) and decylubiquinone with an apparent K(m) for NADH of approximately 17 and 5 muM, respectively. The inhibitory profile of PfNDH2 revealed that the enzyme activity was insensitive to rotenone, consistent with recent genomic data indicating the absence of the canonical NADH:dehydrogenase enzyme. PfNDH2 activity was sensitive to diphenylene iodonium chloride and diphenyl iodonium chloride, known inhibitors of alternative NADH:dehydrogenases. Spatiotemporal confocal imaging of parasite mitochondria revealed that loss of PfNDH2 function provoked a collapse of mitochondrial transmembrane potential (Psi(m)), leading to parasite death. As with other alternative NADH:dehydrogenases, PfNDH2 lacks transmembrane domains in its protein structure, and therefore, it is proposed that this enzyme is not directly involved in mitochondrial transmembrane proton pumping. Rather, the enzyme provides reducing equivalents for downstream proton-pumping enzyme complexes. As inhibition of PfNDH2 leads to a depolarization of mitochondrial Psi(m), this enzyme is likely to be a critical component of the electron transport chain (ETC). This notion is further supported by proof-of-concept experiments revealing that targeting the ETC's Q-cycle by inhibition of both PfNDH2 and the bc(1) complex is highly synergistic. The potential of targeting PfNDH2 as a chemotherapeutic strategy for drug development is discussed.
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PMID:Functional characterization and target validation of alternative complex I of Plasmodium falciparum mitochondria. 1664 58

There are consistent differences in cardiovascular state between acute illness in malaria and recovery that prolong the electrocardiographic QT interval and have been misinterpreted as resulting from antimalarial cardiotoxicity. Of the different classes of antimalarial drugs, only the quinolines, and structurally related antimalarial drugs, have clinically significant cardiovascular effects. Drugs in this class can exacerbate malaria-associated orthostatic hypotension and several have been shown to delay ventricular depolarisation slightly (class 1c effect), resulting in widening of the QRS complex, but only quinidine and halofantrine have clinically significant effects on ventricular repolarisation (class 3 effect). Both drugs cause potentially dangerous QT prolongation, and halofantrine has been associated with sudden death. The parenteral quinoline formulations (chloroquine, quinine, and quinidine) are predictably hypotensive when injected rapidly, and cardiovascular collapse can occur with self-poisoning. Transiently hypotensive plasma concentrations of chloroquine can occur when doses of 5 mg base/kg or more are given by intramuscular or subcutaneous injection. At currently recommended doses, other antimalarial drugs do not have clinically significant cardiac effects. More information on amodiaquine, primaquine, and the newer structurally related compounds is needed.
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PMID:Cardiotoxicity of antimalarial drugs. 1764 28

The results of Fe(2+)-induced decomposition of the clinically used artemisinins, artemisone, other aminoartemisinins, 10-deoxoartemisinin, and the 4-fluorophenyl derivative have been compared with their antimalarial activities and their ability to inhibit the parasite SERCA PfATP6. The clinical artemisinins and artemisone decompose under aqueous conditions to give mixtures of C radical marker products, carbonyl compounds, and reduction products. The 4-fluorophenyl derivative and aminoartemisinins tend to be inert to aqueous iron(II) sulfate and anhydrous iron(II) acetate. Anhydrous iron(II) bromide enhances formation of the carbonyl compounds and provides a deoxyglycal from DHA and enamines from the aminoartemisinins. Ascorbic acid (AA) accelerates the aqueous Fe(2+)-mediated decompositions, but does not alter product distribution. 4-Oxo-TEMPO intercepts C radicals from a mixture of an antimalaria-active trioxolane, 10-deoxoartemisinin, and anhydrous iron(II) acetate to give trapped products in 73 % yield from the trioxolane, and 3 % from the artemisinin. Artemisone provides a trapped product in 10 % yield. Thus, in line with its structural rigidity, only the trioxolane provides a C radical eminently suited for intermolecular trapping. In contrast, the structural flexibility of the C radicals from the artemisinins allows facile extrusion of Fe(2+) and collapse to benign isomerization products. The propensity towards the formation of radical marker products and intermolecular radical trapping have no relationship with the in vitro antimalarial activities of the artemisinins and trioxolane. Desferrioxamine (DFO) attenuates inhibition of PfATP6 by, and antagonizes antimalarial activity of, the aqueous Fe(2+)-susceptible artemisinins, but has no overt effect on the aqueous Fe(2+)-inert artemisinins. It is concluded that the C radicals cannot be responsible for antimalarial activity and that the Fe(2+)-susceptible artemisinins may be competitively decomposed in aqueous extra- and intracellular compartments by labile Fe(2+), resulting in some attenuation of their antimalarial activities. Interpretations of the roles of DFO and AA in modulating antimalarial activities of the artemisinins, and a comparison with antimalarial properties of simple hydroperoxides and their behavior towards thapsigargin-sensitive SERCA ATPases are presented. The general basis for the exceptional antimalarial activities of artemisinins in relation to the intrinsic activity of the peroxide within the uniquely stressed environment of the malaria parasite is thereby adumbrated.
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PMID:The Fe2+-mediated decomposition, PfATP6 binding, and antimalarial activities of artemisone and other artemisinins: the unlikelihood of C-centered radicals as bioactive intermediates. 1776 32


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