Criteria

Centers for Disease Control and Prevention (CDC)

Severe (or complicated) disease is defined as laboratory-confirmed or suspected malaria cases with ≥1 of the following clinical criteria for severe disease:[100]

  • Impaired consciousness, convulsions, or coma

  • Severe anemia (hemoglobin <7 mg/dL)

  • Acute kidney injury

  • Acute respiratory distress syndrome

  • Circulatory collapse/shock

  • Disseminated intravascular coagulation

  • Acidosis

  • Jaundice (plus at least one other sign of severe malaria)

  • Parasite density ≥5%

World Health Organization (WHO)

Uncomplicated disease

  • Presents with symptoms of malaria and a positive parasitologic test (i.e., light microscopy or rapid diagnostic test), but with no features of severe malaria (see below).[49]

Severe (or complicated) disease

According to the World Health Organization (WHO), patients are classified as having severe falciparum malaria if they have one or more of the following (occurring in the absence of an identified alternative cause and in the presence of P falciparum asexual parasitemia):[49]

Clinical features

  • Impaired consciousness (i.e., Glasgow coma score <11 in adults or Blantyre coma score <3 in children)

  • Prostration (i.e., generalized weakness so that the patient is unable to walk or sit up without assistance)

  • Multiple convulsions (more than 2 episodes in 24 hours)

  • Respiratory distress (rapid, deep, labored breathing)

  • Circulatory collapse or shock - systolic blood pressure <80 mmHg in adults and <70 mmHg in children with evidence of impaired perfusion (decompensated shock); capillary refill ≥3 seconds or temperature gradient on leg (mid-to-proximal limb) without hypotension (compensated shock)

  • Significant bleeding (e.g., recurrent or prolonged bleeding from gums, nose, or venepuncture sites; hematemesis; melena)

  • Pulmonary edema (radiologic confirmed, or oxygen saturation <92% on room air with a respiratory rate >30 breaths/minute often with chest indrawing and crepitations on auscultation)

Laboratory findings

  • Hypoglycemia (blood or plasma glucose <40 mg/dL [2.2 mmol/L])

  • Acidosis (base deficit >8 mEq/L [>8 mmol/L]; or if not available, plasma bicarbonate <15 mEq/L [<15 mmol/L] or venous plasma lactate ≥5 mmol/L [≥45 mg/dL])

  • Severe malarial anemia (children ages <12 years: Hb ≤5 g/dL or hematocrit of ≤15%; adults: Hb <7 g/dL or hematocrit of <20%) with a parasite count >10,000/microliter

  • Serum bilirubin >3 mg/dL [>50 micromol/L] with a parasite count >100,000/microliter

  • Hyperparasitemia: parasitemia >10%

  • Renal impairment (plasma or serum creatinine >3 mg/dL [265 micromol/L]) or blood urea nitrogen >56 mg/dL [>20 mmol/L])

Severe P vivax and P knowlesi malaria are defined as for severe falciparum malaria above, but with no parasite density thresholds. Severe P knowlesi malaria is defined as for severe falciparum malaria above, but with two differences:

  • P knowlesi hyperparasitemia: parasite density >100,000/microliter

  • Jaundice and parasite density >20,000/microliter

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