Malaria-associated syndromes
Gazzinelli RT, Kalantari P, Fitzgerald KA, Golenbock DT. Innate sensing of malaria parasites. Nat Rev Immunol. 2014 14(11):744-57.
Syndrome Clinical features Mechanism
Anaemia • Low haemoglobin levels and RBC counts • Rupture of infected RBCs
• Pallor • Removal of infected and altered RBCs by splenic macrophages
• Lethargy often with jaundice • Inhibition of erythropoiesis by cytokines
Systemic inflammation • Alterations in body temperature • Parasite activation of splenic macrophages leads to a systemic inflammatory response (cytokine storm) that is associated with dysfunction of cardiovascular, respiratory, renal, neurological, hepatic, and/or coagulation systems
• Tachycardia • Sepsis-like syndrome leads to acute respiratory distress syndrome
• Rapid breathing, often with impaired gas exchange • Parasitized RBC sequestration causes a disruption of the alveolar–capillary interface, resulting in leukocyte infiltration, and oedema in the interstitium and alveoli, culminating in severe hypoxaemia
• Arterial hypotension
• High levels of lactate in the blood
• Altered mental status
Metabolic acidosis • Hyperventilation • Metabolic acidosis is due to increased glycolysis and the accumulation of lactic acid, in particular during hypoxia caused by anaemia and/or blood vessel obstruction by sequestering parasites
• Hypoxia • Renal dysfunction and insufficient clearance of lactic acid. The lower blood pH stimulates the brainstem to increase the respiratory rate to expel more carbon dioxide, resulting in hypocapnia, which causes vasoconstriction and cerebral hypoxia, thus exa
• Headache
• Altered mental status
• Nausea
• Vomiting
• Abdominal pain
• Muscle weakness
Cerebral malaria • Lethargy • Activation of endothelial cells by circulating pro-inflammatory mediators or by parasite components
• Unbalanced movements • Enhanced expression of adhesion molecules in endothelial cells, parasite sequestration, obstruction of blood flow, intravascular coagulation, disruption of the endothelial barrier integrity, and local tissue inflammation
• Seizures
• Impaired consciousness
• Coma
• Neurological sequelae
Placental malaria • Placental insufficiency • Parasite sequestration and deposition of haemozoin in the intervillous space of the placenta results in the activation of placental macrophages, production of chemokines, recruitment of monocytes, intravascular macrophage differentiation, and production
• Fetal growth retardation
• Low birth weight
• Premature delivery
• Stillbirth
• Miscarriage
• Neonatal and maternal morbidity and mortality
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