Cerebral Malaria

A condition characterized by somnolence or coma in the presence of an acute infection with PLASMODIUM FALCIPARUM (and rarely other Plasmodium species). Initial clinical manifestations include HEADACHES; SEIZURES; and alterations of mentation followed by a rapid progression to COMA. Pathologic features include cerebral capillaries filled with parasitized erythrocytes and multiple small foci of cortical and subcortical necrosis. (From Adams et al., Principles of Neurology, 6th ed, p136)

Also Known As:

Networked: 984 relevant articles (66 outcomes, 130 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Malaria
2.	Parasitemia
3.	Infection
4.	Coma (Comas)
5.	Shock

Experts

1.	Hunt, Nicholas H: 18 articles (02/2016 - 09/2003)
2.	Taylor, Terrie E: 17 articles (01/2015 - 04/2003)
3.	Grau, Georges E: 17 articles (01/2014 - 10/2002)
4.	Molyneux, Malcolm E: 15 articles (01/2015 - 04/2003)
5.	Kain, Kevin C: 15 articles (01/2014 - 01/2006)
6.	Ball, Helen J: 13 articles (02/2016 - 02/2004)
7.	Looareesuwan, Sornchai: 13 articles (09/2010 - 01/2002)
8.	John, Chandy C: 12 articles (07/2015 - 09/2006)
9.	Carvalho, Leonardo J M: 11 articles (10/2015 - 01/2006)
10.	Anstey, Nicholas M: 11 articles (03/2015 - 02/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Cerebral Malaria:

1.	artemetherFDA Link 03/01/1996 - "The clinical efficacy of intramuscular artemether was studied in 144 children suffering from severe non cerebral malaria. " 05/01/1997 - "The disposition of intramuscular artemether in children with cerebral malaria; a preliminary study." 02/12/2005 - "Rectal artemether is effective and well tolerated and could be used as treatment for cerebral malaria." 10/15/1999 - "Artemether represents an important option in the management of cerebral malaria in Nigeria especially in rural areas where facilities for intravenous administration may not yet be optimal." 05/01/1997 - "The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. "
2.	Quinine (Quinson)FDA Link 12/01/1990 - "Quinine is emerging as the only effective treatment for cerebral malaria, though resistance to this drug threatens to become a problem. " 06/01/2002 - "To compare in a randomized study the efficacy and the toxicity of the new WHO intravenous quinine treatment of cerebral malaria including a loading dose regimen to a regimen without loading dose. " 07/01/1998 - "An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger." 01/01/1998 - "The study population consisted of 26 Zambian children < 6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. " 09/01/1994 - "Delay in diagnosis and initiation of treatment with quinine adversely affected the prognosis of cerebral malaria in the study group."
3.	artemisinine (artemisinin)IBA 05/01/2014 - "Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. " 11/01/2013 - "(Sweet Annie or Qinghao) which yields artemisinin (Qinghaosu), effective against cerebral malaria-causing strains of Plasmodium falciparum. " 04/01/2011 - "Artemisinin has rather low toxicity; it is effective against drug-resistant Plasmodium species and against cerebral malaria. " 06/01/1982 - "Clinical studies on treatment of cerebral malaria with qinghaosu and its derivatives." 10/08/2015 - "Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria. "
4.	artesunateIBA 05/01/2005 - "Two clinical studies were conducted using CRDS as adjunct medication to conventional therapy (artesunate) in patients with severe and severe/cerebral malaria. " 12/01/1993 - "This is the first in vivo study to show that artesunate interferes with continued PRBC sequestration in the cerebral microvessels in cerebral malaria.(ABSTRACT TRUNCATED AT 250 WORDS)" 01/01/2014 - "Therefore, it could be helpful and suitable to administer artesunate in the context of cerebral malaria, especially in young children. " 01/01/2013 - "Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria." 05/01/2011 - "Despite parenteral artesunate therapy, the fatality rate of cerebral malaria remains high. "
5.	AntibodiesIBA 04/01/2005 - "These results are consistent with a potential anti-toxin role for anti-GPI antibodies associated with protection against cerebral malaria." 01/01/1996 - "Antibodies disrupting erythrocyte rosettes have been associated with protection against cerebral malaria, and antibodies agglutinating infected erythrocytes with reduced episodes of clinical disease. " 11/01/1992 - "The results suggest that rosettes and anti-rosette formation antibodies formed by squirrel monkeys and humans exhibited similar characteristics, and that the squirrel monkey is therefore a good experimental model to study erythrocyte rosette formation and cerebral malaria." 01/01/1992 - "Clinical trials of treatment with monoclonal anti-TNF antibodies are presently underway in an attempt to reduce mortality and morbidity in african children with cerebral malaria." 04/01/1997 - "Antibodies against parasites of the 3D7 genotype are associated with a better prognosis among children with cerebral malaria partly because these children are more likely to be infected with parasites of this genotype rather than the FC27 genotype, which appears to be more virulent."
6.	Chloroquine (Aralen)FDA LinkGeneric 09/01/1993 - "These observations suggest that chloroquine may help to prevent cerebral malaria whatever the drug sensitivity of the parasite strain, and may provide new tools for an anti-disease therapy regardless of the emergence of parasite multi-drug resistance." 11/01/1991 - "Comparative trial of oral versus intramuscular chloroquine in children with cerebral malaria." 01/15/2013 - "In longitudinal studies, cerebral malaria appeared nearly 1 d earlier in the AQP4-null mice, and reduced survival was noted when chloroquine rescue was attempted. " 12/01/2010 - "Furthermore, these deficits were still evident forty days after cessation of chloroquine, indicating persistence long after successful treatment, a hallmark feature of human cerebral malaria. " 12/01/2010 - "Here we used a chloroquine treatment model of cerebral malaria to determine whether these abnormal outcomes would be persistent in the mouse model. "
7.	arteether (artemotil)IBA 06/01/2002 - "Efficacy of alpha, beta - Arteether in children with cerebral malaria in forested tribal belt." 11/01/1997 - "Plasmodium fragile: efficacy of arteether (alpha/beta) against cerebral malaria model." 04/01/2000 - "A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria." 01/01/2004 - "Both trials compared arteether with quinine in children with cerebral malaria and reported on similar outcomes. " 12/01/1989 - "Pharmacological studies on alpha/beta arteether (a 30:70 mixture of isomers), a potential drug for the treatment of cerebral malaria, were carried out in experimental animals by giving the drug in arachis oil suspension. "
8.	Mefloquine (Lariam)FDA LinkGeneric 01/01/2009 - "Impact of cerebral malaria on brain distribution of mefloquine." 10/01/1999 - "These findings suggest that intragastric mefloquine deserves consideration whenever parenteral drugs are not available for the treatment of cerebral malaria." 10/01/1999 - "Rapid absorption and clinical effectiveness of intragastric mefloquine in the treatment of cerebral malaria in African children." 01/01/1999 - "Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria." 12/01/1992 - "Smear-negative cerebral malaria due to mefloquine-resistant Plasmodium falciparum acquired in the Amazon."
9.	atorvastatin (Lipitor)FDA Link 01/01/2013 - "The objective of this study was to evaluate the in vivo efficacy of Proveblue® when combined with atorvastatin in a murine model of experimental cerebral malaria. " 01/01/2013 - "Combination of atorvastatin with lower doses of Proveblue® (<10 mg/kg/day) should be evaluated to show potential synergistic effects in cerebral malaria prevention." 01/01/2013 - "Atorvastatin alone or in combination appears to possess limited use for preventing cerebral malaria. " 01/01/2013 - "Although there was only one death in the atorvastatin and Proveblue® combination treatment group (10%) versus two deaths (22%) with Proveblue® treatment, the effect on cerebral malaria was not significant (p = 0.283). " 01/01/2013 - "Treatment with Proveblue® or a combination of Proveblue® and atorvastatin was significantly increased survival of cerebral malaria (p = 0.0011 and 0.0002, respectively). "
10.	Tumor Necrosis Factor-alpha (Tumor Necrosis Factor)IBA 04/01/2009 - "The high serum TNF-alpha level that is caused by mutation in the promoter of the TNF-alpha gene is associated with cerebral malaria. " 02/01/2008 - "In children with cerebral malaria, central nervous system TNF-alpha production is associated with subsequent neurologic and cognitive morbidity." 03/01/2007 - "Significant association between TNF-alpha (TNF) promoter allele (-1031C, -863C, and -857C) and cerebral malaria in Thailand." 08/01/2003 - "This article reviews the involvement of TNFalpha in cerebral malaria and the relation with all the processes involved in this pathology. " 08/01/2003 - "Tumor necrosis factor alpha in the pathogenesis of cerebral malaria."

Therapies and Procedures

1.	Enteral Nutrition (Feeding, Tube) 01/01/2011 - "A randomized trial of early (day of admission) versus late (after 60 hours in adults or 36 hours in children) start of enteral feeding was undertaken in patients with cerebral malaria in Chittagong, Bangladesh from May 2008 to August 2009. " 01/01/2011 - "Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial." 01/01/2011 - "In conclusion, early start of enteral feeding is detrimental in non-intubated patients with cerebral malaria in many resource-poor settings. " 01/01/2011 - "There is equipoise whether early enteral feeding is also beneficial in non-intubated patients with cerebral malaria in resource poor settings. "
2.	Intranasal Administration 01/01/2014 - "Efficacy of intranasal administration of artesunate in experimental cerebral malaria." 01/01/2014 - "In this study, intranasal administration of artesunate to rescue from cerebral malaria using a murine model was tested. "
3.	Drug Therapy (Chemotherapy) 01/01/2009 - "Cerebral malaria carries an unacceptable case fatality rate in children despite timely and adequate chemotherapy. " 12/01/1996 - "Chemotherapy for cerebral malaria." 05/01/1990 - "During the same period, parasitaemia in 13 patients with cerebral malaria treated with chemotherapy alone showed little reduction from initial levels of 0.20-1.74 X 10(6)/microliters (11-42 per cent). " 10/20/2015 - "The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15-25% in African children despite effective antimalarial chemotherapy. " 11/01/2003 - "Some patients with Plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. "
4.	Chelation Therapy (Therapy, Chelation) 03/01/1998 - "Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria." 01/01/1997 - "These data are consistent with the hypothesis that iron chelation therapy in children with cerebral malaria strengthens Th1-mediated immune effector function involving increased production of NO." 05/01/2001 - "Iron chelation therapy of Plasmodium falciparum infection alleviates the clinical course of cerebral malaria in children. " 11/19/1992 - "Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria." 11/19/1992 - " It is concluded that iron chelation therapy may speed the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria."
5.	Renal Dialysis (Hemodialysis) 02/01/1999 - "Eleven of the patients who died were jaundiced and eight of them had cerebral malaria with a Glasgow Coma Score < or = 8. We conclude that hemodialysis is a useful treatment for oliguric and nonoliguric ARF from severe malaria, particularly when initiated early in the course of the illness." 03/01/1998 - "In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. " 02/01/1994 - "All of them had evidence of intrahepatic cholestasis and needed hemodialysis for several weeks; 7 survived and 2 died, one due to cerebral malaria, the other multiple organ failure. " 10/02/2000 - "These longitudinal data suggest that: (i) severe falciparum malaria is associated with skeletal muscle damage that increases during initial therapy especially in patients with coma; (ii) the effect of other major treatment or infection-specific factors that are associated with muscle damage does not diminish this relationship; and (iii) cerebral malaria in combination with a high baseline and rising serum CK should pre-empt monitoring and management strategies aimed at preserving renal function including renal dialysis." 03/01/1998 - " There were no significant differences between groups in terms of parasite and fever clearance time, recovery time from coma in patients with cerebral malaria, duration of intubation in patients with respiratory distress, number of hemodialysis treatments required for patients with acute renal failure, or number of units of blood administered to patients in need of transfusion. "