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Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria
Georges E Grau1, Charles D Mackenzie, Richard A Carr
1Experimental Parasitology Unit, IFR48, Université de la Méditerranée, Marseille, France. georges.grau@medecine.univ-mrs.fr
Abstract:
The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
Insights
Platelets accumulate in brain blood vessels in fatal cerebral malaria (CM). This finding in human patients suggests platelets may contribute to the severe disease pathology.
Area of Science:
- Neurology
- Hematology
- Infectious Diseases
Background:
- The exact causes of fatal cerebral malaria (CM) remain unclear, with limited patient data available.
- Previous studies in mouse models indicated that platelets accumulating in brain microvasculature could improve outcomes with antiplatelet therapy.
Purpose of the Study:
- To investigate the presence and role of platelets in the cerebral microvasculature of children who died from cerebral malaria.
- To compare platelet accumulation in cerebral vessels between CM patients and non-CM controls.
Main Methods:
- Immunohistopathology was used to detect platelet glycoprotein GPIIb-IIIa in brain tissue samples from Malawian children.
- Tissue samples were analyzed from patients with severe malarial anemia, CM, and nonmalarial encephalopathy.
- Quantification of platelet staining surface area and the proportion of affected vessels was performed.
Main Results:
- Platelets were identified within cerebral microvessels in three distinct patterns: interspersed with malaria pigment and leukocytes, associated with malaria pigment, or isolated.
- Significantly higher mean surface area of platelet staining was observed in CM patients compared to non-CM cases.
- A greater proportion of cerebral vessels showed evidence of platelet accumulation in patients with CM.
Conclusions:
- Platelet accumulation is a significant feature of the cerebral microvasculature in fatal human cerebral malaria.
- These findings support the hypothesis that platelet aggregation plays a role in the pathogenesis of cerebral malaria.