Cerebral malaria
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Cerebral Malaria. severe complication of falciparum malaria mortality of 30-50% associated with sequestration in micro-vasculature of brain a diffuse encephalopathy with loss of consciousness consciousness ranges from stupor to coma unresponsive to pain, visual, and verbal stimuli

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Cerebral malaria

Cerebral Malaria

  • severe complication of falciparum malaria

    • mortality of 30-50%

  • associated with sequestration in micro-vasculature of brain

  • a diffuse encephalopathy with loss of consciousness

    • consciousness ranges from stupor to coma

    • unresponsive to pain, visual, and verbal stimuli

    • convulsions frequently observed

    • onset can be gradual or sudden


Cerebral malaria

Complications Associated with Falciparum Malaria

  • cerebral malaria

  • anemia

  • hyperpyrexia

  • hypoglycemia

  • acidosis

  • GI and liver syndromes

  • pulmonary edema

  • blackwater fever

  • algid malaria (shock)


Cerebral malaria

Features Indicating Poor Prognosis in Severe Malaria

  • impaired consciousness

  • repeated convulsions

  • respiratory distress

  • shock

  • acidosis/hyperlactemia

  • hypoglycemia

  • jaundice or other liver malfunctions

  • renal impairment

  • high parasitemia (>500,000/mm3)


Cerebral malaria

Higher Parasitemias in Falciparum Malaria

  • all erythrocytes invaded

    • Pv/Po = reticulocytes

    • Pm = senescent RBC

  • up to 36 merozoites

  • sequestration of infected erythrocytes

    • trophozoite and schizont stages

    • primarily in brain, heart, lungs, and gut

    • complications

    • immune evasion


Cerebral malaria


Cerebral malaria

P. falciparum expresses ‘knobs’ on the surface of infected erythrocytes. Knobs mediate cytoadherence to endothelial cells.


Cerebral malaria

Several Parasite Proteins Are Associated with Knobs

  • KAHRP and PfEMP2 are believed to interact with the submembrane cytoskeleton of the host erythrocyte

  • reorganization of the membrane skeleton may result in knob formation

  • PfEMP1 crosses the erythrocyte membrane and is exposed on the surface


Cerebral malaria

PfEMP-1 Structure

  • family of 40-50 var genes

  • conserved intracellular C-terminus

    • acidic terminal segment (ATS)

    • binds cytoskeleton + KAHRP

  • transmembrane domain

  • variable extracellular domain composed of modules

    • 2-7 copies of Duffy-binding like domains

      • 5 sequence types (a, b, g, d, e)

    • 1-2 cys-rich interdomain regions

    • all have DBL1a + CIDR

  • participates in cytoadherence


Cerebral malaria

Possible Host Receptors

  • CD36

  • Ig super-family

    • ICAM-1

    • VCAM-1

    • PECAM-1

  • E-selectin

  • thrombospondin

  • chondroitin sulfate A

  • hyaluronic acid

  • Rosetting Receptors

    • CR-1

    • glycosaminoglycan

    • blood group A


Cerebral malaria

Sequestration

Hypothesis

cytoadherence

cerebral ischemia

hypoxia, metabolic effects

coma

death


Cerebral malaria

Problems with Sequestration Hypothesis

  • rapid reversibility

  • lack of ischemic damage

  • low levels of permanent neurological damage

  • sequestration occurs in non-cerebral malaria cases



Cerebral malaria


Cerebral malaria

  • Severe falciparum malaria

  • potentially high parasitemias

  • sequestration

  • complex (and not fully understood) host-parasite interactions