Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
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Co-infection with falciparum malaria and leptospirosis is uncommon. The aim of this study is to report a case of severe sepsis secondary to dual infection with falciparum malaria and leptospirosis. The literature is also reviewed on the clinical course of such co-infections, and the possible mechanisms and treatment of patients with life-threatening malaria and leptospirosis with activated protein C. The patient was a 25-year old male admitted in the Respiratory Intensive Care Unit (RICU) with fever, haemolysis, acute renal failure, hepatitis, acute lung injury (ALI) and altered sensorium. A syndromic evaluation was done and investigations revealed falciparum parasitaemia. He was treated with parenteral artesunate, ceftriaxone and doxycycline, and adjunctive therapies as for severe sepsis. Infusion of activated protein C was started 20 hours after onset of organ dysfunction, and intensive haemodialysis was instituted. Over the next four days the patient became afebrile with progressive resolution of ALI, renal failure and hepatitis. His Leptospira serology (requested as part of the evaluation) was reported positive on day 5. Dual infections are common and under-recognized in the tropics. Failure to treat potential co-infections may lead to poor outcomes. Acute lung injury in falciparum malaria has high mortality rates and therapy as for severe sepsis may improve survival. Adjunctive therapies, including activated protein C, cannot replace source eradication.
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PMID:Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C. 1742 47

This review summarizes the origins of the insight that excess production of pro-inflammatory cytokines caused a constellation of changes that contribute to pathophysiology of disease. This connection was made following the original 1975 TNF (tumor necrosis factor) publication from New York describing how activated macrophages kill tumors. The study caught the eye of a group in London who were trying to understand how the same in vivo macrophage activation would protect mice against the erythrocytic protozoan parasites that cause malaria and babesiosis. Based on collaborative research between these two groups, it was argued in 1981 that TNF and related cytokines initiated events that caused pathology, as well as parasite death within red cells in these infectious diseases. This proved to be a key conceptual advance. It was also argued that the pathology of bacterial sepsis logically had TNF origins. Once TNF was cloned in 1985, allowing its specific analysis in serum and neutralization in vivo, the involvement of this cytokine in infectious disease pathology was pursued by a number of groups. Some researchers found that once "their" cytokine was cloned and sequenced, they had been unwittingly expanding knowledge on TNF for several years. By the late 1980s excess TNF production was proposed to be central to acute systemic viral diseases. This family of cytokines is now at the centre of investigations to understand the mechanisms of acute systemic viral diseases, including influenza and the hemorrhagic viral diseases. With its implication as the master regulator of other inflammatory cytokines in the synovial membrane, TNF has also become the major cytokine in the pathogenesis of chronic inflammatory disease. Its neutralization has proven to be a potent treatment for rheumatoid arthritis and Crohn's disease.
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PMID:How TNF was recognized as a key mechanism of disease. 1749 63

There is renewed interest in the potential contribution of community health workers to child survival. Community health workers can undertake various tasks, including case management of childhood illnesses (eg, pneumonia, malaria, and neonatal sepsis) and delivery of preventive interventions such as immunisation, promotion of healthy behaviour, and mobilisation of communities. Several trials show substantial reductions in child mortality, particularly through case management of ill children by these types of community interventions. However, community health workers are not a panacea for weak health systems and will need focussed tasks, adequate remuneration, training, supervision, and the active involvement of the communities in which they work. The introduction of large-scale programmes for community health workers requires evaluation to document the impact on child survival and cost effectiveness and to elucidate factors associated with success and sustainability.
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PMID:Achieving child survival goals: potential contribution of community health workers. 1758 87

A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multi-organ failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.
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PMID:The use of activated protein C in severe Plasmodium falciparum malaria. 1759 Nov 42

Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte-macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur.
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PMID:Blood coagulation in falciparum malaria--a review. 1806 97

Clinical and epidemiologic surveillance of malaria cases and deaths is required to follow the progress of the reinvigorated malaria control programs nationally and internationally. Current recording, transmittal, analysis, feedback, and use of malaria surveillance information is delayed and imprecise: substantially < 10% of the malaria cases and deaths are being reported. Improvements are occurring, but more emphasis should be placed on prompt, accurate diagnosis, patient management, and recording of clinical manifestations at hospitals. Neurologic signs, severe anemia, metabolic changes, hyperparasitemia, and concurrent sepsis are medical emergencies and require proper clinical and laboratory detection; equipment, reagents, supervision, and certification of laboratorians and clinicians are necessary. Birth weight should also be a major measure of progress in malarial control and overall prenatal care. Although malaria is the most frequent diagnosis at outpatient clinics and hospitals in Africa, co-existing conditions also mandate improved diagnosis, treatment, and registration. Monthly transmittal of information from health units and collation, analysis and feedback through electronic reporting systems using modern information technologies are necessary for resource planning and staff motivation. Denominators to compute rates of illness and death require accurate censuses of communities from which patients come to health units: specialized disease and demographic household surveys designed and performed by nationals are needed to complement hospital-based numerator data. Plasmodium falciparum and P. vivax should be distinguished in the laboratory; the former causes the greatest mortality but the latter is increasingly recognized as a major peril. Because vector control is now a major component of all malaria control programs, there is an urgent need to monitor anopheline sensitivity to insecticides and entomologic inoculation rates. Where interrupting transmission is a goal, parasite rates in groups at greatest risk should be performed. Continual monitoring of plasmodial sensitivity to drugs is necessary using WHO protocols. Human, entomological, and parasitological surveillance must be performed at the same time in the same places and the information shared widely and used for improving control strategies and tactics. These surveillance priorities require training, provision of equipment, supervision, and commitment to sustainability by national authorities and international collaborators and donors.
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PMID:Malaria surveillance counts. 1816 73

Acute renal failure (ARF) is a common problem in the Congo. This is a six-year retrospective study aiming at analyzing the etiology and the outcome of ARF at the Brazzaville's University Hospital from 1989 through 1994. One hundred and five cases of ARF (0.99%), including 54 boys (51.4%) and 51 girls (48.6%), out of 10,512 children admitted in the department of Pediatrics have been recorded. ARF represented 13.09% of the causes in 802 patients with renal disorder. The main etiologies of ARF included acute gastroenteritis with dehydration (25.7%), nephrotic syndrome (14.7%), sepsis (15.23%), malaria (12.38%), and acute glomerulonephritis (9.5%). Most cases were managed conservatively, while peritoneal dialysis (PD) was used in eight cases (7.62%). The outcome of ARF was recovery in 50.5 %, death in 37 % and chronic renal failure in 12.5% of cases. Preventive measures may help in reducing the high mortality rate and the need for dialysis.
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PMID:Etiology and outcome of acute renal failure in children in congo-brazzaville. 1820 97

Acute kidney injury (AKI) has become increasingly prevalent in both developed and developing countries, and is associated with severe morbidity and mortality, especially in children. Uncertainty regarding the true incidence of AKI limits awareness of the problem, thereby reducing political visibility of the disorder and hampering efforts to prevent its occurrence. In developed countries, AKI occurs predominantly in urban intensive care units and is associated with multiorgan failure and sepsis, high mortality, and occurrence in older populations. While cases of AKI in urban areas of the developing world have similar characteristics to those in the developed world, AKI in rural regions commonly develops in response to a single disease and specific conditions (e.g. gastroenteritis) or infections (e.g. severe malaria, leptospirosis, or hemolytic-uremic syndrome) and in younger otherwise healthy individuals. Many causes of AKI in rural settings, such as diarrhea, poisoning, malaria, or septic abortion, can be prevented by interventions at the individual, community, and regional levels. Treatment with dialysis is often unavailable or too costly in developing regions, so there must be community-wide efforts to eradicate causes of AKI, expedite diagnosis, and aggressively manage prerenal conditions and specific infections. We have reviewed recent literature on AKI, identified differences and similarities in the condition between developed and developing areas, analyzed the practical implications of the identified differences, and made evidence-based recommendations for study and management.
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PMID:The contrasting characteristics of acute kidney injury in developed and developing countries. 1821 80

It is now broadly accepted for infectious disease in general that it is not the invading organism, but the body's unbridled response to it--the "cytokine storm"--that causes illness and pathology. Nevertheless, many researchers still regard the harmful effects of falciparum malaria as being governed by oligaemic hypoxia arising from parasitised erythrocytes obstructing blood flow through vulnerable organs, particularly the brain, and we summarise why these notions are no longer tenable. In our view, this harmful sequestration is readily accommodated within the cytokine storm perspective as one of its secondary effects. We approach these issues by examining aspects of malaria, sepsis and influenza in parallel, and discuss the insights that comparisons of the literature can provide on the validity of possible anti-disease therapies.
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PMID:Understanding the role of inflammatory cytokines in malaria and related diseases. 1834 78

Acute bilateral renal cortical necrosis is a rare cause of renal failure frequently induced by disseminated intravascular coagulation (Dic) following obstetrical complications, sepsis and drugs. We describe a case of Dic with bilateral cortical necrosis after ingestion of only one tablet of quinine. A 41-year-old woman was admitted for severe abdominal pain, melaena, fever and anuria two hours after quinine tablet intake for nocturnal leg cramps. Her medical history included angioneurotic edema caused by chloroquine for malaria prevention. Physical examination was normal. Laboratory data showed acute renal failure, hemolytic anemia without schistocytes and Dic. Platelet antibodies were negative. Ultrasonographic examination showed a complete defect of renal perfusion with permeable renal arteries. Results of abdominal CT scan and MAG3 scintigraphy led to the diagnosis of bilateral renal cortical necrosis. The patient underwent plasma exchanges with fresh frozen plasma which induced rapid resolution of Dic. She remained dependent on chronic hemodialysis. Quinine-induced microangiopathic hemolytic anemia and Dic is a rare described entity. These complications occur typically in quinine-sensitized subjects. The presence of acute renal failure is generally associated with poor prognosis in case of bilateral renal cortical necrosis. Caution is required for the prescription of quinine derivates, which should be avoided in patients experienced on adverse reaction to the drug.
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PMID:[Quinine-induced renal bilateral cortical necrosis]. 1834 36


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