Malaria, Cerebral

Publication Title: 
Bulletin of the World Health Organization

A total of 141 cases of strictly defined cerebral malaria were studied in a controlled trial of three regimens: (1) intramuscular artemether plus oral mefloquine, (2) intravenous artesunate plus oral mefloquine, and (3) intravenous quinine (with or without an initial loading dose) plus oral tetracycline. The overall mortalities in each group were 14%, 8.3% and 34.3% respectively. The average parasite clearance time was 27.30 +/- 19.62 hours in regimen 1, 41.84 +/- 17.55 hours in regimen 2, and 47.30 +/- 21.95 hours in regimen 3.

Author(s): 
Win, K.
Than, M.
Thwe, Y.
Publication Title: 
The Journal of Infectious Diseases

Plasma concentrations of big endothelin-1 were determined by ELISA in 18 patients with complicated Plasmodium falciparum malaria in Bangkok. Before therapy, elevated levels were recorded (21 +/- 12 vs. 2.9 +/- 1.1 pmol/L in age- and sex-matched healthy subjects; P < .001). Even 7 days after therapy, elevated concentrations were seen (25 +/- 14 pmol/L). Plasma endothelin levels were correlated with levels of tumor necrosis factor-alpha (r = .632, P < .01), and a negative correlation with platelet counts was seen (r = .783, P < .005).

Author(s): 
Wenisch, C.
Wenisch, H.
Wilairatana, P.
Looareesuwan, S.
Vannaphan, S.
Wagner, O.
Graninger, W.
Schönthal, E.
Rumpold, H.
Publication Title: 
The Journal of Antimicrobial Chemotherapy

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice.

Author(s): 
Prada, J.
Müller, S.
Bienzle, U.
Kremsner, P. G.
Publication Title: 
The New England Journal of Medicine

BACKGROUND: Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance. Artemether is a new antimalarial agent that clears parasites from the circulation more rapidly than quinine, but its effect on mortality is unclear. METHODS: We conducted a randomized, unblinded comparison of intramuscular artemether and intramuscular quinine in 576 Gambian children with cerebral malaria. The primary end points of the study were mortality and residual neurologic sequelae.

Author(s): 
van Hensbroek, M. B.
Onyiorah, E.
Jaffar, S.
Schneider, G.
Palmer, A.
Frenkel, J.
Enwere, G.
Forck, S.
Nusmeijer, A.
Bennett, S.
Greenwood, B.
Kwiatkowski, D.
Publication Title: 
Tropical medicine & international health: TM & IH

OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children. METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here.

Author(s): 
Taylor, T. E.
Wills, B. A.
Courval, J. M.
Molyneux, M. E.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Clinical investigation of malaria is hampered by the lack of a method for estimating the number of parasites that are sequestered in the tissues, for it is these parasites that are thought to be crucial to the pathogenesis of life-threatening complications such as cerebral malaria. We present a method of estimating this hidden population by using clinical observations of peripheral parasitemia combined with an age-structured mathematical model of the parasite erythrocyte cycle.

Author(s): 
Gravenor, M. B.
van Hensbroek, M. B.
Kwiatkowski, D.
Publication Title: 
The Journal of Infectious Diseases

Plasma levels of interleukin (IL)-6, soluble IL-6 receptor, soluble gp130, leukemia inhibitory factor (LIF), and ciliary neutrophic factor (CNTF) were analyzed in 32 patients with severe malaria. Ten had renal failure, 8 had cerebral malaria, and 14 had other causes of severity. Before treatment, the IL-6 and soluble IL-6 receptor plasma levels were significantly higher in persons with cerebral malaria or renal failure than in other groups (P<.01 for both). After initiation of therapy, IL-6 levels dropped within 24 h, but soluble IL-6 receptor levels increased.

Author(s): 
Wenisch, C.
Linnau, K. F.
Looaresuwan, S.
Rumpold, H.
Publication Title: 
Journal of Neurology, Neurosurgery, and Psychiatry

Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogeneous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern.

Author(s): 
Newton, C. R.
Hien, T. T.
White, N.
Publication Title: 
Antimicrobial Agents and Chemotherapy

We report the first detailed pharmacokinetic assessment of intrarectal (i.r.) artesunate (ARS) in African children. Artesunate was given intravenously (i.v.; 2.4 mg/kg of body weight) and i.r. (10 or 20 mg/kg formulated as 50- or 200-mg suppositories [Rectocaps]) in a crossover study design to 34 Ghanaian children with moderate falciparum malaria. The median relative bioavailability of dihydroartemisinin (DHA), the active antimalarial metabolite of ARS, was higher in the low-dose i.r. group (10 mg/kg) than in the high-dose i.r. group (20 mg/kg) (58 versus 23%; P = 0.018).

Author(s): 
Krishna, S.
Planche, T.
Agbenyega, T.
Woodrow, C.
Agranoff, D.
Bedu-Addo, G.
Owusu-Ofori, A. K.
Appiah, J. A.
Ramanathan, S.
Mansor, S. M.
Navaratnam, V.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens.

Author(s): 
Thuma, P. E.
Bhat, G. J.
Mabeza, G. F.
Osborne, C.
Biemba, G.
Shakankale, G. M.
Peeters, P. A.
Oosterhuis, B.
Lugt, C. B.
Gordeuk, V. R.

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