Severe Falciparum Malaria in Children Current Understanding of Pathophysiology and Supportive Treatment

Newton, Charles R.; Krishna, Sanjeev

doi:10.1016/s0163-7258(98)00008-4

Cited by 295 publications

(259 citation statements)

References 323 publications

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“…The pathogenesis of CM is poorly understood, but cerebral pathology is associated with the sequestration of mature parasitized RBCs (pRBCs) in the microvasculature of tissues (2,3). This characteristic feature of P. falciparum infection serves as an immune evasion strategy by the parasite that prevents the removal of pRBCs in the spleen, thus facilitating parasite survival (3)(4)(5). Although advantageous for the parasite, this strategy concentrates malaria parasites, and the metabolic and inflammatory responses triggered by them, in vital organs such as the brain (6).…”

mentioning

confidence: 99%

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Amante

Haque

Stanley

et al. 2010

The Journal of Immunology

156

180

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mentioning

confidence: 99%

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Amante

Haque

Stanley

et al. 2010

The Journal of Immunology

156

180

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“…1 The pathogenesis of childhood cerebral malaria is not well understood. 2 A central occurrence in the production of the clinical syndrome is adherence of parasitized erythrocytes to endothelial cells of the cerebral vasculature. This initiates a cascade of events that cause intense endothelial activation on the luminal side of the blood-brain barrier.…”

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confidence: 99%

Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism?

Dobbie¹,

Crawley²,

Waruiru³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an agematched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] ϭ 14.1 [9.8-20.4], P Ͻ 0.001) and total neopterin (10.9 [9.1-13.0], P Ͻ 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations were decreased (geometric mean ratio ϭ 0.45 [0.35-0.59], P Ͻ 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.Cerebral malaria is the most serious complication of infection with Plasmodium falciparum, which causes the death of more than 1 million children in sub-Saharan Africa each year. 1 The pathogenesis of childhood cerebral malaria is not well understood. 2 A central occurrence in the production of the clinical syndrome is adherence of parasitized erythrocytes to endothelial cells of the cerebral vasculature. This initiates a cascade of events that cause intense endothelial activation on the luminal side of the blood-brain barrier. 3 These events include cytoadherence itself, 4 and the production of inflammatory cytokines, 5-7 malarial toxins, 8 and nitric oxide.9-12 Much less is known about events occurring on the abluminal side of the blood-brain barrier in cerebral malaria and the cause of cerebral symptoms.The clinical syndrome of childhood cerebral malaria is characterized by the rapid onset and recovery from a diffuse encephalopathy. 13 The coma is complicated by raised intracranial pressure and seizures occur in more than half the patients. 14,15 Between 5% and 15% of survivors of cerebral malaria have neurologic sequelae suggesting focal brain damage. 16,17 These clinical findings could be explained by an excitotoxic mechanism.Experimental stimulation of cells of the macrophage/ monocyte lineage by various cytokines causes the parallel induction of indoleamine-pyrrole 2,3-dioxygenase (EC 1.13.11.42, indoleamine 2,3-dioxygenase), GTP cyclohydrolase I (EC 3.5.4.16), and nitric oxide synthase (EC 1.14.13.39). 18,19 These enzymes catalyze the first step of pathways that lead to the formation of quinolinic acid, neopterin and tetrahydrobiopterin, and nitric oxide, respectively. In the brain, microglia constitute the resident macrophage/ monocyte cells. Experimental stimulation of microglia with cytokines also causes induction of these enzymes. 20,21 Quinolinic acid is an endogenous excitotoxin that is a selective agon...

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“…Serebral malarya tablosu nadir görü-lür; P. falciparum ile daha sık görülmekte ve ölüm oranı %4-46 olarak bildirilmektedir (17,18). Serebral sıtma genellikle hızlı gelişir.…”

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Plasmodium falciparum Malaria Case Originating from Uganda

Altun¹,

Gul²,

Vudali³

et al. 2013

TurkiyeParazitolDerg

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ÖZETSıtma dünyada en sık ölüme yol açan enfeksiyonlar arasında beşinci sırada yer almaktadır. Plasmodium türlerinin insan hücrelerini infekte ederek sıtmaya neden olan P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi olmak üzere beş türü bulunmaktadır. Dünya Sağlık Örgütü verilerine göre Uganda, malarya açısından en yüksek insidansa sahip ve her yıl 1000 insandan 478'inin sıtmaya yakalandığı bir ülkedir. Bu makalede Uganda'ya yaptığı iş seyahati sonrası P. falciparum'un etken olduğu bir malarya olgusu değerlendirildi. Hastanın başlıca klinik bulguları üşüme-titreme ve yüksek ateşti. Periferik kandan hazırlanan ince yayma ve kalın damla kan preparatlarının incelenmesi sonucunda P. falciparum parazitemisi saptandı. Bilinci, oryantasyon ve kooperasyonu bozulan hastada serebral sıtma düşünüldü. Tedavi sonrası belirgin bir şekilde klinik iyileşme gözlenen hastanın yapılan kontrol kan yaymasında parazite rastlanmadı. (Turkiye Parazitol Derg 2013; 37: 229-32) Anahtar Sözcükler: Plasmodium falciparum, Uganda, seyahat öyküsü, kemoprofilaksi Geliş Tarihi: 23.09.2012Kabul Tarihi: 01.03.2013 ABSTRACTMalaria is the fifth infection leading to death in the world. Plasmodium species is the malarial parasite that infects human cells. The five species of the human Plasmodium parasites are P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. Recently, the World Health Organization reported that Uganda has the world's highest malaria incidence, with a rate of 478 cases per 1000 population per year. In this article, a patient who had specific clinical signs and symptoms of malaria after work-related travel to Uganda has been evaluated. The major clinical findings of the patient were chills and fever. After examination of thin and thick blood smears prepared from the peripheral blood of the patient, P. falciparum parasites were observed. Cerebral malaria was suspected as the patient's consciousness, orientation and cooperation had deteriorated. No Plasmodium was seen in control blood smears after treatment. (Turkiye Parazitol Derg 2013; 37: 229-32) Bir protozoon hastalığı olan sıtmada klinik tablo, düzenli aralıklarla gelen ateş ve titreme ile karakterizedir. Plasmodium falciparum'un etken olduğu infeksiyonda tipik ateş ve titreme nöbetleri 48 saatte bir gözlenmektedir (5). Serebral sıtma, akut böbrek yetmezliği, hipoglisemi, ağır anemi, splenomegali ve akciğer ödemi diğer sıtma etkenlerine göre daha sık olarak gözlenmekte ve mortaliteyi artırmaktadır (6).

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Severe Falciparum Malaria in Children Current Understanding of Pathophysiology and Supportive Treatment

Cited by 295 publications

References 323 publications

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism?

Plasmodium falciparum Malaria Case Originating from Uganda

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