الملخص
Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
الموضوعات
Child , Adult , Humans , Antimalarials/pharmacology , Cardiovascular Diseases/drug therapy , Artemisinins/pharmacology , Quinolines , Malaria, Cerebral/drug therapy , Heart Failure/drug therapy , Arrhythmias, Cardiac/drug therapyالملخص
Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.
الموضوعات
Humans , Adjuvants, Pharmaceutic/administration & dosage , Antimalarials/administration & dosage , Curcumin/administration & dosage , Malaria, Cerebral/drug therapyالملخص
Albumin, the principal transporter of plasma fatty acids, binds to majority of the drugs ingested, traps oxygen radicals and has potent anti-oxidant actions. Albumin binds to its specific binding sites on vascular endothelial cells and thus, prevents endothelial apoptosis. Albumin regulates the enzyme pyruvate dehydrogenase, the flux of glucose and lactate in astrocytes, and enhances the formation of anti-inflammatory lipoxins, resolvins and protectins from docosahexaenoic acid (DHA) and other polyunsaturated fatty acids that, in turn, could limit ischemia-induced neuronal damage. This may explain the beneficial action of DHA-enriched albumin in stroke and other critical diseases. ©
الموضوعات
Albumins/therapeutic use , Critical Illness/therapy , Docosahexaenoic Acids/therapeutic use , Humans , Malaria, Cerebral/drug therapy , Neuroprotective Agents/therapeutic use , Sepsis/drug therapyالملخص
Cerebral malaria is the most common cause of non-traumatic encephalopathy in the world. The mainstay of therapy is either quinine or artemisinin, both of which are effective antimalarials. The clinical picture of cerebral malaria may persist or even become worse in spite of the clearance of parasites from blood. The death rate is unacceptably high even with effective antimalarials in tertiary care hospitals. The mortality increases in presence of multi organ failure (renal failure, jaundice, respiratory distress, severe anaemia, lactic acidosis, etc.). The pathogenesis of cerebral malaria is multifactorial and includes clogging, sequestration, rosette formation, release of cytokines, cerebral oedema, increased intracranial hypertension, etc. Attempts are made to use adjuvant therapy which will act through alternate mechanisms and address one or more of the pathogenetic processes. In this review, we have discussed the role of corticosteroids, pentoxifylline, desferrioxamine, mannitol and newer agents in the treatment of cerebral malaria. Though the literature on adjuvant therapy in cerebral malaria is large enough, there are a number of shortcomings in the clinical trials, many being open and non randomized or of very small sample size. Further research is of utmost importance through large multicentric, double-blind controlled trials to show the efficacy of any of these drugs.
الموضوعات
Adrenal Cortex Hormones/therapeutic use , Antimalarials/therapeutic use , Blood-Brain Barrier/physiopathology , Chemotherapy, Adjuvant/methods , Deferoxamine/therapeutic use , Humans , Malaria, Cerebral/drug therapy , Mannitol/therapeutic use , Pentoxifylline/therapeutic useالملخص
In the present day scenario of resurgence of infectious diseases, malaria compounded with problems of multi drug resistance, assumes paramount importance. A combination of artemisinine derivatives with other effective anti-malarial drug remains the most effective form of treatment against the falciparum malaria which is most lethal form of disease. Oral chloroquin in the dose of 25 mg base/kg over 48 hours is effective in infections due to P. vivax, P. ovale P. malariae and chloroquine sensitive P. Falciparum. For chloroquine resistant P. vivax and multidrug resistant falciparum malaria, a combination of Quinine with doxycycline or clindamycin for 5-7 days, Quinine with singlt dose sulfadoxine-pyrimethamine combination. Mefloquine with artemeter or artesunate for 3 days, artesunate with doxycycline or clindamycin for 7 days and Otovaquin with proguanil for 3 days have been found to be effective. Primiquin as a hypnozoticide for 5-10 days is mandatory for preventing relapse in cases of P. vivax, P. Ovale and P. malariae. Death due to complicated malaria can be as high as 75% if case diagnosis is delayed or the patient arrives late. The artemisinine based rectal suppositories can be very effective in home/village setting in patients who can not be given oral anti malarial, though not yet approved for use in our country. In ICU settings, properly administered loading dose of quinine has proved to be effective and safe in almost all therapeutic trials including our study on Indian patients. Frequent blood glucose monitoring is mandatory. Parentral artemisinine with oral mefloquine is an effective alternative to quinine based therapy. The cerebral malaria management in the ICU setting includes monitoring fluid and electrolyte balance so as to maintain a CVP of 5 cm of water and pulmonary arterial occlusive pressure at less than 15 mm of mercury. In renal failure haemofiltration is ideal. Mefloquine is safe in second and third trimester of pregnancy. Exchange transfusion, haemopheresis and plasmapheresis are new techniques in the treatment of gravely ill patients with PF malaria especially when parasitemia exceeds 10%.
الموضوعات
Animals , Antimalarials/adverse effects , Child , Child, Preschool , Female , Humans , Malaria/complications , Malaria, Cerebral/drug therapy , Plasmodium/classification , Pregnancy , Pregnancy Complications, Parasitic/drug therapyالملخص
We report the effectiveness of two regimens of rectal artesunate formulation in treating 13 Thai children with cerebral/complicated falciparum malaria. The drug was given at an initial dose of 40 mg/kg bodyweight, in 3 or 4 divided doses in the first 24 hours, followed by 10 mg/kg bodyweight once daily for three consecutive days. Mefloquine, at a dose of 15 mg/kg bodyweight was given orally at 72 hours after the initial dose of artesunate, followed by 10 mg/kg bodyweight 6 hours later. Three cases with cerebral malaria gained consciousness within 20 hours of artesunate administration. The median time required for reduction of parasitemia by 90% of the initial value (P90) in 13 children was 11.2 hours. No recrudescence was observed in any of the patients during the 28-day follow-up period. Plasma concentrations of artesunate and dihydroartemisinin (active plasma metabolite of artesunate) measured in two patients who received the high initial dose regimen (20 mg/ kg bodyweight) suggested rapid absorption and adequate plasma concentrations of both compounds following the administration of artesunate via the rectal route. Further studies for the optimized regimen of rectal artesunate in the treatment of cerebral/complicated childhood falciparum malaria in areas of multidrug resistance are warranted.
الموضوعات
Administration, Rectal , Animals , Antimalarials/administration & dosage , Artemisinins/administration & dosage , Child , Child Welfare , Child, Preschool , Drug Resistance, Multiple , Drug Therapy, Combination , Humans , Malaria, Cerebral/drug therapy , Malaria, Falciparum/drug therapy , Mefloquine/administration & dosage , Plasmodium falciparum/drug effects , Sesquiterpenes/administration & dosage , Suppositories , Thailand , Treatment Outcomeالملخص
Human cerebral malaria is caused by a protozoan parasitic with no cure till date. The isolation of brain capillaries i.e. microvessels has permitted the in vitro study related to cerebral function. Microvessels were isolated from normal and P. yoelii infected mice brain cortex and subjected to biochemical characterization by the following enzyme markers viz alkaline phosphatase, gamma-glutamyI transpeptidase and monoamine oxidase and electron microscopically. Limited studies have been carried out in relation to drug metabolizing enzymes in cerebral microvessels of rodents. The present studies have been carried out in relation to status of drug metabolizing enzymes during P. yoelii infection in cerebral microvessels of mice. The data obtained depicted a clear cut impairment of cytochrome P450 (a terminal monooxygenase) and related indices viz b5, benzopyrene hydroxylase, aminopyrene-n-demethylase, aniline hydroxylase except NADH cytochrome e reductase which increased during P. yoelii infection in mice as compared to normal. Further the oral drug administration (arteether) treatment brought back the altered MFO system normal a week alter cessation of drug treatment.
الموضوعات
Animals , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Brain/enzymology , Disease Models, Animal , Malaria, Cerebral/drug therapy , Mice , Muscle, Smooth, Vascular/drug effects , Plasmodium yoeliiالملخص
Two cases of cerebral malaria imported from Guyana and Ghana are reported. These are the first cases of cerebral malaria diagnosed and treated in Trinidad and Tobago since malaria was eradicated. The management of both these cases was complicated because the patients' erythrocytes were glucose-6-phosphate dehydrogenase-deficient, and by the occurrence of blackwater fever, cerebral manifestations, renal impairment, hyperglycaemia and thrombocytopenia. The symptoms of cerebral malaria resolved following treatment with quinidine and doxycycline and quinidine and clindamycin.
الموضوعات
Adult , Humans , Middle Aged , Glycogen Storage Disease Type I/complications , Malaria, Cerebral/complications , Plasmodium falciparum , Travel , Malaria, Cerebral/diagnosis , Malaria, Cerebral/drug therapy , Immunity, Innateالملخص
Embora nao esteja definitivamente comprovada que a severidade da malária esteja associada com o vírus da imunodeficiência humana (HIV), sabe-se que a infecçao pelo Plasmodium falciparum pode favorece uma rápida evoluçao da infecçao pelo HIV. Além disso a associaçao da malária com HIV/AIDS, do ponto de vista clínico, pode ser extremamente grave face a ocorrência de outros microorganismos e/ou neoplasias, o que piora a evoluçao e prognóstico dos pacientes. A concomitância do vírus HIV com o Plasmodium em zonas endêmicas de malária, é uma possibilidade que deve ser sempre pensada, visto que a sua transmissao está relacionada a fatores de risco ligados aos comportamentos das pessoas, que nem sempre sao logo revelados e/ou identificados. Os autores descrevem um caso de malária cerebral Plasmodium vivax e Plasmodium falciparum em um paciente com AIDS. Descrevem sua evoluçao clínica e terapêutica.
الموضوعات
Humans , Male , Adult , Malaria, Cerebral/complications , Acquired Immunodeficiency Syndrome/complications , Enzyme-Linked Immunosorbent Assay , Malaria, Cerebral/diagnosis , Malaria, Cerebral/drug therapy , Acquired Immunodeficiency Syndrome/diagnosisالموضوعات
Humans , Male , Female , Malaria, Cerebral/drug therapy , Malaria, Cerebral/complications , Malaria, Cerebral/mortality , Child , Antimalarials , Quinineالملخص
La malaria cerebral puede producir gran variedad de síntomas y signos. Presentamos 14 casos diagnósticados en el Hospital Regional del Sur y en el bloque Materno Infantil del Hospital Escuela, Honduras, de agosto de 1970 a mayo de 1995. Los pacientes se presentaron con síntomas y signos de encefalopatía aguda con conducta psicótica, convulsiones y fiebre. La malaria cerebral debida a Plasmodium vivax ocurrió en 71//de los casos. Todos los pacientes fueron tratados con cloroquina y en 12 casos también con primaquina. Dos pacientes fueron tratados con amodiaquina. Dos pacientes murieron, uno con daño cerebral severo y otro con hipovolémico más neumonía bilateral
الموضوعات
Child , Chloroquine/therapeutic use , Malaria, Cerebral/complications , Malaria, Cerebral/drug therapy , Plasmodium vivaxالملخص
Twelve cases of cerebral malaria due to plasmodium falciparum, treated with loading dose of quinine (20 mg/kg salt in 500 ml of 5% glucose infused IV in 4 hrs) are compared with eleven age and sex matched cases treated with conventional dose of 10 mg/kg. The parasite clearance rate was significantly faster in loading dose group. There was no difference in recovery time: the interval between the initiation of treatment to full recovery of consciousness in both groups. One patient had pretreatment hypoglycaemia and two cases in the conventional dose group developed hypoglycaemia during therapy. One patient died in conventional dose group due to multi-organ failure. Two litres blood exchange transfusion was also tried for this case. Mild cinchonism occurred in two cases after loading dose while this was observed only in one case in conventional dose group. There was no significant hypotension or ECG changes in any patient. Loading dose of quinine seems to be well tolerated and may clear parasitaemia faster in case of malaria due to Plasmodium falciparum (PF).