Falciparum malaria causes severe life-threatening complications. Summarized in the table are the manifestations of severe malaria.

Manifestations of severe falciparum malaria
I Cerebral malaria
II Severe anemia
III Pulmonary edema
IV ARDS (acute respiratory distress syndrome)
V Renal insufficiency
VI Disseminated intravascular coagulation
VII Hypoglycemia
VIII Metabolic Acidosis
IX Septic shock (superinfection)

Fig1. Sequestration in brain microvessels

Fig2. Sequestration of schizont

Cerebral malaria
Even with correct treatment the mortality from cerebral malaria is 15%. Every year, cerebral malaria kills 0.5-1 million children.
In order to understand the pathogenesis of cerebral malaria it is important to recall that
1. P. falciparum often (not always) causes high parasitemia
2. P.falciparum is uniquely capable to adhere to brain microvessel endothelium (sequestration).
Massive sequestration (Fig1-2) impairs cerebral blood flow and induces immune inflammatory response leading to brain edema and serious sequalae.
For practical purposes, cerebral malaria can be defined as any impairment of consciousness or convulsions in a patient exposed to malaria. Non-specific symptoms may persist several days before the global impairment of consciousness, followed by coma, emerge. Coma in cerebral malaria is unrouseable (Glasgow Coma Score, 10/14) and usually persists more than 6 hrs after generalized convulsion.
Convulsions in malaria manifest as partial motor seizures and they are considered as a bad prognostic sign.
Progression to deep coma from prostration and convulsions can be rapid.
Generally, the diagnosis of cerebral malaria may be only ascertained after excluding other possible causes of prolonged impaired consciousness:

  1. Other malaria manifestations
    1. hyponatremia
    2. hypoglycemia
    3. multi-organ failure etc.
  2. Other infections (may co-exist)
    1. meningitis
    2. sepsis
  3. Metabolic diseases (diabetes)
  4. Other neurologic diseases
  5. Head trauma
Treatment of cerebral malaria is complex depending on the manifestations. Intravenous quinine (see Malaria Treatment for details) is an effective option. Alternative treatment includes intravenous or rectal artemisinin or artesunate. Anti-convulsive therapy should be initiated only if absolutely indicated because it may potentially worsen the existing depression of respiration. All patients with cerebral malaria should be ideally managed and monitored in the intensive care unit (ICU). Hypoglycemia should be avoided, electrolyte derangement should be corrected and all vital functions have to be ensured.

Modified Glasgow Coma Scale: Unrousable coma is < 10 (for children see the Blantyre coma scale)
Eyes open
to speech
to pain

Best verbal response
inappropriate words
incomprehensive sounds

Best motor response
obeys commands
localized pain
flexion to pain
extension to pain

Total 3-14

Severe anemia
Severe anemia is another big killer of young children (< 2 years old) in endemic P.falciparum regions throughout the world. Severe anemia is also common in pregnant women (see Malaria in Pregnancy). According to some statistic, about 10% of adults are anemic (Hb < 7g/dl) on their admission to the hospital for malaria. The severe anemia is usually correlated with the degree of parasitemia, which is often quite high in falciparum malaria. Numerous infected erythrocytes are destroyed during shcyzogony. But this is not the only cause of anemia. Erythrophagocytosis by enlarged spleen (hypersplenism) depletes not only IgG-coated infected erythrocytes but often intact erythrocytes contributing to the pathogenesis of severe anemia (Fig3.). Additionally, bone marrow is also suppressed, though reversibly.

Fig3. Infected and non-infected erythrocyte destruction

Usually severe anemia has a prolonged duration. The lab results for hemoglobin are below 5 mg/dl (< 3 mmol/L). Hemolysis is classically accompanied by hyperbilirubinemia and hemoglobinuria. Effective anti-malarial treatment ensures parasite clearance and restoration of bone marrow function. The usefulness of blood transfusion has been quite controversial in management of severe malaria and high parasitemia. However, exchange blood transfusion can be still considered if parasitemia overexceeds 20%. Overall blood circulation and oxygenation should be optimized. Urinary output has to be kept high, and precautions should be taken while the fluids are loaded to avoid precipitating pulmonary edema. Our quick recommendation on the laboratory investigations at the ICU would include:

  1. blood smears (x3, monitoring of parasitemia)
  2. blood culture for sepsis
  3. Hb, thrombocytes, WBC + differential counts 4. Na, K, creatinine
  4. bilirubin, ASAT, LDH, Factors II-VII-X
  5. glucose
  6. arterial blood gases, lactate.

More information on severe malaria and its treatment can be found in the WHO edition of Management of Severe Malaria, and also in the article by Wilairatana P., et al. "Guideline in management of severe malaria".

Case Study
53 year old male civil engineer, resident in Ghana for 6 years.
No malaria prophylaxis due to fear of side effects (and general opposition toward doctors)
During field work feeling feverish, treated with aspirin
Returned after 5 days. Wife finds the patient extremely ill looking and rushes him to hospital
On arrival pale, acutely ill, tp. 41.2oC, slow cerebrated
Blood film: 17% P. falciparum (ring stages)
Hb 8.2 g/dl, thrombocyte count 46, WBC normal range
Creatinine 320 mmol/l, Na 120 mmol/l, K 4.0 mmol/l, Glucose 3.8 mmol/l
Treatment suggestion?

  • Quinine 10 mg/kg infusion in 5% dextrose/saline over 4 h stat.
  • Quinine 10 mg/kg infusion tds
  • After parasite clearance (marked reduction) continue oral quinine at same dosage for 7 days
    • Alternatively doxycycline 100 mg/day for 7 days
    • Never use mefloquine after quinine (may increase myocardial toxicity)
    Other necessary measures?
  • Hyponatraemia treated with isotonic saline and frusemide
  • Renal function did not deteriorate but was normalised after rehydration
  • Follow blood glucose carefully
  • Thrombocytes normalised after parasite clearance


© 2002. Malaria in Armenia.
Designed by Ghazanchyan.com