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)

Cerebral involvement during malaria is a complication that leads to seizure, coma, and death. The effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. Erythropoietin (EPO) is one of the more promising drugs in this area. We measured the effect of EPO on the survival of mice infected with Plasmodium berghei ANKA and demonstrated that inoculations of recombinant human EPO at the beginning of the clinical manifestations of cerebral malaria protect >90% of mice from death. This drug has no effect on the course of parasitemia. The effect of EPO was not related to either the inhibition of apoptosis in the brain or the regulation of the increase and decrease of nitric oxide production in the brain and blood, respectively. Tumor necrosis factor-alpha and interferon-gamma mRNA overexpression was inhibited by EPO, and treated mice had fewer brain hemorrhages. EPO has been used in patients with chronic diseases for years, and more recently it has been used to treat acute ischemic stroke. The data presented here provide the first evidence indicating that this cytokine could be useful for the symptomatic prevention of mortality during the acute stage of cerebral malaria.
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PMID:Recombinant human erythropoietin prevents the death of mice during cerebral malaria. 1739 15

Plasmodium falciparum and human immunodeficiency virus type 1 (HIV-1) infections are common in children living in sub-Saharan Africa (SSA). Both of these pathogens affect the central nervous system (CNS). Most HIV-1 infection of children in this region is acquired from infected mothers, particularly during breast-feeding and at the time of delivery. Over a third of children infected by birth will have died before their first birthday, before overt CNS manifestations have developed. The most common manifestations of primary CNS infection include neurodevelopmental delay, impaired brain growth, motor deficits, and behavioral problems. These deficits may also result from infections, neoplasm, or stroke. Cognitive impairments become more evident if the child survives for longer, but in Africa, children rarely survive past their fifth birthday. In malaria endemic areas, severe falciparum malaria usually develops after 6 months of age, and most of the CNS manifestations are more common in children over 1 year old. About 11% of children develop neurological deficits following cerebral malaria, most of which improve within 2 years of the insult. However, up to 24% of children may have neurocognitive impairments following severe malaria. The effect of milder malaria and coincidental parasitization on cognitive function is unknown. Other comorbidities that are common in SSA, such as malnutrition or micronutrient deficiencies, may influence children's neurodevelopment. The coinfection of malaria and HIV-1 may aggravate the neurodevelopmental impairments documented in these children. However, to date there are little published data, although it may have a profound effect of children living in SSA.
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PMID:Interaction between Plasmodium falciparum and human immunodeficiency virus type 1 on the central nervous system of African children. 1654 Apr 55

Stroke is a global epidemic and an important cause of morbidity and mortality. It ranks next to cardiovascular disease and cancer as a cause of death. "India is likely to suffer huge social and economic burden in the rehabilitation of stroke patients owing to increased life expectancy" and urbanization. Though, there are national programs in malaria eradication and tuberculosis control, there is hardly any governmental support in stroke management and rehabilitation. We propose to formulate stroke-prevention strategies specific to our national needs and covering all the age groups. Allocation of resources towards the stroke management and research is needed. Emphasis on stroke awareness in community should be stressed and should be inclusive of means of primordial and primary prevention apart from management of stroke and its recurrence. Recent international experience in stroke management has suggested the need of specialized stroke units (comprehensive stroke care under one roof). We wish to establish the need of creating awareness regarding the urgency of specialized care in acute stroke. We also wish to motivate our national health institutions to offer affordable, evidence based management of stroke and offer opportunities in stroke training and research.
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PMID:Comprehensive stroke care: an overview. 1664 38

At the joint meeting of the Australasian Society of Clinical and Experimental Pharmacology and the Australasian Pharmaceutical Sciences Association, held December 4-7, 2005, in Melbourne, Australia, and other select meetings, drugs for the treatment of the overactive bladder, benign prostatic hyperplasia, cancer, stroke, pain, malaria and cardiovascular disease were discussed. During these discussions, the following possible drug targets were considered: urothelium-derived inhibitory factor, muscarinic receptors in the bladder, purinergic signaling, pacemaking cells in the urogenital tract, cannabinoid receptors in the prostate, vascular endothelial growth factor in cancer, the nonselective cation channel TPRV1 in pain, and angiotensin receptors, Rho kinase, connective tissue growth factor and NADPH oxidase in cardiovascular disease.
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PMID:Pharmacology down under in 2005--focus on targets. 1682 99

The HIV/AIDS pandemic is creating a strain on health care services in the developing world, with knock-on consequences for HIV negative patients. We looked for possible changes over time in the patterns of illness and outcomes of admission to an adult medical unit in Zimbabwe. We performed a prospective descriptive study of discharge diagnoses and causes of in-hospital ;mortality for all medical patients under the care of one consultant at Mpilo Central Hospital, Bulawayo, Zimbabwe. Two similar 7-month periods were compared in 1992 and 2000. Data recorded included: initials, sex, alive or dead status, diagnosis and HIV/AIDS status. Similar numbers of patients were admitted in 1992 and 2000 (1305 and 1369), but in-hospital mortality increased from 13.3% to 28.6% (P < 0.001), especially in male patients (13.1% to 33.9% P < 0.001). Mortality rates increased for both infectious and non-communicable diseases such as cardiac failure, stroke and diabetes. The 10 most common diagnoses were similar, apart from Pneumocystis carinii pneumonia (PCP) cases, which increased from 18 to 90. The proportion of patients clinically or serologically positive for HIV/AIDS rose from 13.9% to 51.1% (P < 0.001), but the number of cases of the HIV wasting syndrome (SLIM)/chronic gastroenteritis did not change significantly. In 1992 there happened to be a large number of cases of malaria transmission. Mortality related to both communicable and non-communicable diseases increased, confirming that HIV negative patients are also being affected by the strain on health services. Although based on clinical and radiological diagnosis, PCP pneumonia appears to be increasingly common in this area.
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PMID:Increase in hospital mortality from non-communicable disease and HIV-related conditions in Bulawayo, Zimbabwe, between 1992 and 2000. 1688 12

Any planning process for health development ought to be based on a thorough understanding of the health needs of the population. This should be sufficiently comprehensive to include the causes of premature death and of disability, as well as the major risk factors that underlie disease and injury. To be truly useful to inform health-policy debates, such an assessment is needed across a large number of diseases, injuries and risk factors, in order to guide prioritization. The results of the original Global Burden of Disease Study and, particularly, those of its 2000-2002 update provide a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability: the disability-adjusted life-year (DALY). Globally, it appears that about 56 million deaths occur each year, 10.5 million (almost all in poor countries) in children. Of the child deaths, about one-fifth result from perinatal causes such as birth asphyxia and birth trauma, and only slightly less from lower respiratory infections. Annually, diarrhoeal diseases kill over 1.5 million children, and malaria, measles and HIV/AIDS each claim between 500,000 and 800,000 children. HIV/AIDS is the fourth leading cause of death world-wide (2.9 million deaths) and the leading cause in Africa. The top three causes of death globally are ischaemic heart disease (7.2 million deaths), stroke (5.5 million) and lower respiratory diseases (3.9 million). Chronic obstructive lung diseases (COPD) cause almost as many deaths as HIV/AIDS (2.7 million). The leading causes of DALY, on the other hand, include causes that are common at young ages [perinatal conditions (7.1% of global DALY), lower respiratory infections (6.7%), and diarrhoeal diseases (4.7%)] as well as depression (4.1%). Ischaemic heart disease and stroke rank sixth and seventh, retrospectively, as causes of global disease burden, followed by road traffic accidents, malaria and tuberculosis. Projections to 2030 indicate that, although these major vascular diseases will remain leading causes of global disease burden, with HIV/AIDS the leading cause, diarrhoeal diseases and lower respiratory infections will be outranked by COPD, in part reflecting the projected increases in death and disability from tobacco use.
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PMID:Measuring the global burden of disease and epidemiological transitions: 2002-2030. 1689 50

The pathogenesis of cerebral malaria, a major complication of Plasmodium falciparum infection, relies on mechanisms such as cytokine production and cytoadherence of parasitized red blood cells (PRBCs) on microvascular endothelial cells. In this way parasites avoid spleen clearance by sequestration in post-capillary venules of various organs including the brain. Infected erythrocytes adhesion has also been shown to have molecular signaling consequences providing insight on how tissue homeostasis could be comprised by endothelium perturbation. Our previous work demonstrated that PRBCs adhesion to human lung endothelial cells (HLEC) induces caspases activation, oxidative stress and apoptosis. Cytoplasmic Cu/Zn superoxide dismutase (SOD1), which provides the first line of defense against oxidative stress within a cell, is now used as a treatment of numerous diseases including traumatic brain injury and ischemic stroke. In this report, we demonstrated that transient supplementation of SOD1 protects endothelial cells against P. falciparum induced oxidative stress and apoptosis. We also showed a significant decrease in PRBCs cytoadherence through a downregulation of ICAM-1 and an induction of iNOS. Protection of endothelium via antioxidant delivery may constitute a relevant strategy in cerebral malaria treatment.
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PMID:Transient supplementation of superoxide dismutase protects endothelial cells against Plasmodium falciparum-induced oxidative stress. 1693 Jul 39

A case-series study of all admissions using patient registers was carried out to analyse patterns of medical admissions into the Medical Intensive Care Unit (MICU) of the Addis Ababa University Teaching Hospital, and evaluate for any changes in that pattern over a study period. All patients admitted to the MICU of a 500-bed Teaching Hospital in Addis Ababa between 1985-2000 were the study subjects. Demographic variables, specific categories of diagnoses and their outcomes were recorded A total of 3548 patients (male to female ratio of 1.4:1, mean age 37.10 +/- 17.29) were admitted from September 1985 to August 2000. Acute infectious and cardiovascular diseases accounted for half of the entire critical care admissions with infectious diseases accounting for 30%. Among specific diagnoses, diabetic ketoacidosis was the leading cause of admission followed by acute myocardial infarction and severe and complicated malaria, each accounting for 10.7, 9.8 and 9.3% of all admissions respectively. Trends of admissions over the sixteen-year period showed steady increase in relative frequency of acute complications of non-communicable diseases consisting of diabetes, acute myocardial infarction and stroke while infectious diseases showed interspersed peaks of admissions coinciding with epidemics. The overall mortality of the MICU was 32%, with proportionally more female deaths, 34.8 versus 29% (P = 0.0002). Severe and complicated malaria was the leading cause of death (10.3%) followed by tetanus (6.4%) and acute myocardial infarction (6.3%). The increase in relative and absolute frequency of acute complications of non-communicable diseases most probably heralds an emerging epidemic of non-communicable diseases related to life style changes in the urban well to do in addition to existing problems of infectious diseases of poverty.
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PMID:Pattern of admissions to the medical intensive care unit of Addis Ababa University Teaching Hospital. 1744 61

Sickle cell disease (SCD) is a genetic blood disorder caused by abnormal hemoglobin that damages and deforms red blood cells (RBCs). The abnormal red cells break down, causing anemia, and obstruct blood vessels, leading to recurrent episodes of severe pain and multiorgan ischemic damage. SCD affects millions of people throughout the world and is particularly common among people whose ancestors come from sub-Saharan Africa. Sickle cell trait (SCT) is an inherited condition in which both normal hemoglobin and sickle hemoglobin are produced in the RBCs. SCT is not a type of sickle cell disease. People with SCT are generally healthy. In SCD, clinical severity varies, ranging from mild and sometimes asymptomatic states to severe symptoms requiring hospitalization. Symptomatic treatments exist, but there is no cure for SCD. Although there has been extensive clinical and basic science research in SCD, many public health issues, such as blood safety surveillance, compliance with immunizations, follow-up of newborns with positive screening tests, stroke prevention, pregnancy complications, pain prevention, quality of life, and thrombosis, in people with SCT remain unaddressed. Currently, efforts are under way to strengthen SCD-related activities within the Centers for Disease Control and Prevention (CDC). To date, several activities are being or have been conducted by centers within CDC, including quality assurance of newborn screening tests for SCD, morbidity and mortality studies, genetic studies, and studies focusing on the protective effects of SCT for malaria. This paper discusses the public health implications of SCD, summarizes SCD-related activities within CDC, and points to future directions that the agency can take to begin to address some of these issues.
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PMID:Sickle cell disease: current activities, public health implications, and future directions. 1762 95

Cerebral malaria is the most severe and rapidly fatal complication of Plasmodium falciparum infection. Despite appropriate anti-malarial treatment using quinine or artemisinin derivatives, 10-20% of mortality still occurs during the acute phase. To improve cerebral malaria outcome, adjunctive therapies are clearly needed. Most experiments in this area have been dedicated to immuno-modulation with various successes. Since erythropoietin has been shown to be highly effective in human ischemic stroke and in murine cerebral malaria, we addressed the issue of cerebral malaria outcome improvement by erythropoietin-artesunate drug combination. Compared to the previous study using erythropoietin high doses at the early beginning of the disease, erythropoietin treatment was decreased by six-fold and delayed to the pre-mortem phase. We studied effects on survival and on clinical recovery of the drug combination given from day 6 to day 8 post-infection to CBA/J mice infected by Plasmodium berghei ANKA. We showed that the artesunate-erythropoietin drug combination led to clinical recovery 24 h earlier for surviving mice, and to increase in the global survival rate compared to artesunate monotherapy (p<0.01). Since erythropoietin has no effect on parasite clearance, it could be stated that this drug combination is efficient and that erythropoietin could be a lead for the implementation of a new adjunctive therapy during the acute phase of cerebral malaria.
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PMID:Artesunate-erythropoietin combination for murine cerebral malaria treatment. 1835 68


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