Cerebral Malaria

Shikani, Henry J.; Freeman, Brandi; Lisanti, Michael P.; Weiss, Louis M.; Tanowitz, Herbert B.; Desruisseaux, Mahalia S.

doi:10.1016/j.ajpath.2012.08.010

Cited by 73 publications

(40 citation statements)

References 74 publications

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“…Most severe malaria deaths in children are due to three overlapping clinical syndromes, malaria with impaired consciousness (cerebral malaria), malaria with respiratory distress due to severe metabolic acidosis and severe anemia (153). Although the pathophysiology is incompletely understood, severe cerebral malaria, one of the most deadly forms of severe malaria, is associated with ischemia caused by sequestration of iRBC in the brain and microvascular damage, edema, blood brain barrier breakdown, and immune cell activation and recruitment resulting in inflammation and oxidative stress (reviewed in (154, 155)). Indeed, in children the pathology of severe disease has been consistently linked to excessive inflammatory responses including the production of the pro-inflammatory cytokines TNF-α, INF-γ, IL-1β and IL-6 and a linked reduced production of the anti-inflammatory cytokine IL-10.…”

Section: Human Immunity and Malariamentioning

confidence: 99%

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Crompton

Moebius

Portugal

et al. 2014

Annu. Rev. Immunol.

257

248

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Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease.

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Section: Human Immunity and Malariamentioning

confidence: 99%

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Crompton

Moebius

Portugal

et al. 2014

Annu. Rev. Immunol.

257

248

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“…The sequestration of P. falciparum -infected erythrocytes in cerebral vessels is the most well-known feature (24). This sequestration is triggered by the expression of P. falciparum erythrocyte membrane protein 1 (PfEMP1) on the cell membrane of malaria-infected erythrocytes, which binds to the cell adhesion molecules (CAMs) such as CD36, ICAM-1 (CD54), and colony-stimulating activity (CSA) on vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Although the findings from numerous animal experiments have greatly contributed to the understanding of cerebral malaria, the observations regarding human cerebral malaria remain limited (24). MRI is expected to improve the understanding of cerebral malaria (28).…”

Section: Discussionmentioning

confidence: 99%

Steroid Pulse Therapy May Mitigate Prolonged Neurological Manifestations after Eradication of Severe <i>Plasmodium falciparum</i> Parasitemia

et al. 2016

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A 58-year-old Japanese man with a high parasitemia of Plasmodium falciparum, returning from Uganda, was admitted to our hospital since his consciousness level rapidly deteriorated after the initial dose of mefloquine. Despite the parasitemia was cleared by quinine by day 7, the coma remained unchanged and diffuse leukoencephalopathy was detected on magnetic resonance image. Steroid pulse therapy was initiated on day 8. Subsequently, the neurological manifestations improved and he was discharged on day 73 without any sequelae. Pathogenesis of P. falciparum causing cerebral malaria is diverse and complex. If neurological symptoms unusually prolong, steroid may be an effective treatment option.

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“…Endothelial damage can cause vascular leakage. In combination with microvessel obstruction due to microcirculatory disturbance, this can lead to cerebral involvement [19]. ICAM-1 and VCAM-1 play a major role as receptors on endothelial cells for P. falciparum-infected erythrocytes, indicating vascular injury [20].…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study

Stauga

Hahn

Brattig

et al. 2013

Malar J

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BackgroundFor rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria.MethodsIn a prospective case-control study, 79 adult travellers with both uncomplicated and complicated P. falciparum malaria were included between 2007 and 2011. Forty-one healthy subjects were included as controls. Blood samples were obtained within 24 hours after first consultation to assess routine laboratory values as well as markers related to inflammation (PAPP-A, copeptin, CRP), endothelial activation (MPO, elastase-2, endothelin-1, sICAM-1, sVCAM-1), cardiac function (NT-proBNP, MR-proANP), coagulation (fibrinogen, D-dimers, platelet count), and haemolysis (LDH). Prognostic performance was assessed using the receiver operating characteristic curve (area under the curve = AUROC).ResultsTwelve (15.2%) patients had severe P. falciparum malaria. In the patient group, significant thrombocytopaenia was found, all other markers but PAPP-A were significantly elevated. Diagnostic performance was best for CRP with an AUROC of 1.00, followed by MPO (0.99), D-dimers (0.98), elastase-2 (0.98), and sICAM-1 (0.98). Biomarker levels did not correlate well with disease severity.ConclusionThe combination of travel history, fever prior to blood sampling, and CRP serum levels above or below 10.8 mg/l upon hospital admission, best discriminated between malaria patients and control persons. None of the biomarkers studied predicted the presence or the development of malaria complications, neither at the time of admission, nor during hospitalization.

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Cerebral Malaria

Cited by 73 publications

References 74 publications

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Steroid Pulse Therapy May Mitigate Prolonged Neurological Manifestations after Eradication of Severe <i>Plasmodium falciparum</i> Parasitemia

Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study

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