Complications of severe falciparum malaria Morbidity and mortality of P. falciparum species is greatest among the malaria species because of its increased parasetemia and its ability to cytoadhere Mortality rises once vital organ dysfunction occurs or proportion of erythrocytes infected increases to >3% P. falciparum is also known for developing drug resistance to chloroquine, quinine and tetracycline

Complications Cerebral malaria Hypoglycemia Lactic acidosis Noncardiogenic pulmonary edema Renal impairment Hematologic abnormalities Liver dysfunction

Cerebral malaria Coma: characteristic & ominous feature of falciparum malaria; mortality rate of ~0.1%, but if there is vital-organ dysfunction, mortality rises steeply Manifests as diffuse symmetric encephalopathy Eyes may be divergent Muscle tone increase or decrease ~15% have retinal hemorrhages Convulsions: generalized; occur up to 50% of children with cerebral malaria

Cerebral malaria ~15% of children with cerebral malaria have been reported to suffer neurologic deficit when they regain consciousness: – Hemiplegia – Cerebral palsy – Cortical blindness – Deafness – Impaired cognition and learning

Hypoglycemia Common complication of severe malaria Associated with poor prognosis Particularly problematic in children and pregnant women Results from a failure of hepatic gluconeogenesis & an ↑ in the consumption of glucose both by host & the malaria parasites Quinine & quinidine are powerful stimulants of pancreatic insulin secretion

Lactic acidosis Commonly coexists with hypoglycemia Caused by combination of: – Anaerobic glycolysis in tissues where sequestered parasites interfere with microcirculatory flow – Hypovolemia – Lactate production by the parasites – Failure of hepatic and renal lactate clearance Coexisting renal impairment compounds acidosis Acidotic breathing: sign of poor prognosis Plasma concentrations of bicarbonate or lactate: best biochemical prognosticators in severe malaria

Noncardiogenic pulmonary edema Mortality rate: >80% Aggravated by overly vigorous administration of IV fluid Can also develop in otherwise- uncomplicated vivax malaria (recovery is usual)

Renal impairment Rare among children May be related to RBC sequestration interfering with renal microcirculatory flow & metabolism Manifests as acute tubular necrosis Early dialysis or hemofiltration enhances the likelihood of a patient’s survival, particularly in acute hypercatabolic renal failure

Hematologic Abnormalities Anemia – results from accelerated RBC destruction & removal by the spleen in conjunction with ineffective erythropoiesis – both infected & uninfected RBCs show reduced deformability – ↑ splenic clearance of RBCs Slight coagulation abnormalities & mild thrombocytopenia

Liver Dysfunction Severe jaundice – more common among adults than children – Results from hemolysis, hepatocyte injury, and cholestasis Hepatic dysfunction contributes to hypoglycemia, lactic acidosis, and impaired drug metabolism