This is probably the CICM examiners' most favourite parasitosis. In the CICM exams, malaria questions tend to ask about the diagnostic tests, acute complications, markers of severity, and antimicrobial management options. It has been asked about in multiple SAQs, which were mostly answered very well:

Malaria is the first topic of Sivakumar and Pelly's chapter on tropical diseases in Oh's Manual. A good 2012 review article can also be found in the Malaria Journal; an older but more detailed review from 2003 is available from Critical Care. A brief summary of these three sources is presented below.


This is the generic list of features. For the "severe malaria" section, the list of features is borrowed from the WHO severity definitions, abridged for easier recall.

Clinical Features of Malaria

Uncomplicated Malaria

  • Fever (cyclical, every 3-4 days)
  • Myalgia
  • Headache
  • Hepatosplenomegaly
  • Jaundice

Severe Malaria

  • Coma
  • Generalised weakness ("prostration")
  • Seizures
  • Acidosis and tachypnoea (mainly a lactic acidosis)
  • Shock
  • Haemolysis, haemoglobinuria and anaemia
  • Hepatic failure
  • DIC
  • Pulmonary oedema or ARDS
  • Acute renal failure
  • High parasite titer

Risk factors for severe malaria:

  • Young age
  • Non-immune travellers
  • Pregnancy

Risk factors for death from malaria

  • Young age (under 3)
  • Cerebral malaria
  • Organ system failure
  • Shock, circulatory collapse
  • Severe anaemia
  • High urea (> 60) and creatinine (>265)

The original full-scale WHO list of criteria for severe malaria can be found in this 2012 review article from the Malaria Journal, as Table 1.

Oh's chapter also lists some differentials (as " alternative explanations" of the more common clinical features), which the savvy candidate will be familiar with. Specifically, "cerebral malaria" can mimic several other meningitis and encephalitis syndromes. Fortunately it has several discriminating features.

Differentials for a malaria-like illness

  • Dengue, or another haemorrhagic fever
  • Typhoid fever
  • Meningitis of any aetiology
  • Hepatitis of whatever viral aetiology
  • Leptospirosis
  • "Relapsing Fever" (Borrellia recurrentis.)


Specific features of cerebral malaria

  • Symmetrical pyramidal signs
  • Retinal findings:
    • Retinal haemorrhages
    • Cotton wool spots
    • Papilloedema
    • Retinal whitening
    • Retinal vessel abnormalities


Thick and thin films

  • Gold standard of diagnosis
  • Thin films allow the identification of specific parasites within the red cells (this way you can identify the species of parasite)
  • Thick films allow a parasite count to be performed
  • Labor-intensive (20 minutes of microscopy)

Rapid diagnostic tests (RDTs)

  • Looking for specific antigens:
    • Parasite species-specific lactate dehydrogenase(pLDH)
    • Aldolase
    • Histidine-rich protein 2 (HRP2) - P.falciparum specific
  • Quick and easy to perform
  • No information about the parasite load
  • Sensitivity and specificity decrease at low parasitaemia.

Malaria PCR

  • Looks for parasite DNA
  • More sensitive than microscopy at identifying malaria
  • More expensive
  • No information about the parasite load

Why do we care about the parasite load?

  • High parasite load is associated with more complications among the non-immune hosts.
  • However, severe complications can still occur with low parasite counts.

Complications of malaria

From the box describing the marks of severe malaria, one can deduce the sort of organ system problems one may develop. The list below is organised according to a familiar A, B, C, D template.

Complications of Severe Malaria




  • ARDS
  • Pulmonary oedema


  • Shock, circulatory collapse
  • Cardiac failure due to anaemia
  • Haemorrhagic shock due to coagulopathy or splenic rupture


  • Generalised weakness
  • Decreased level of consciousness
  • Increased ICP
  • Seizures
  • Hepatic encephalopathy


  • Hypoglycaemia
  • Hyperkalemia
  • Hyponatremia
  • Acidosis (predominantly, lactic)
  • Rhabomyolysis


  • Haemoglobinuria, leading to acute tubular necrosis
  • Acute renal failure due to circulatory collapse
  • ATN due to rhabdomyolysis


  • Hepatosplenomegaly
  • Splenic rupture
  • Hepatic failure
  • GI tract bleeding


  • Disseminated intravascular coagulation
  • Thrombocytopenia
  • Haemolytic anaemia


  • Hyperpyrexia (temperatures over 40°C)


  • The 2010 WHO recommendations suggest a combination treatment. It has be summarised in those blue boxes in the Manual (Boxes 73.1, 73.2 and 73.3 on page 745)

Uncomplicated P.falciparum malaria

First-line alternatives

  • Artesunate  + amodiaquine
  • Artesunate  + sulfadoxine–pyrimethamine
  • Artemether–lumefantrine
  • Dihydroartemisinin plus piperaquine

Second-line alternatives

  • Artesunate plus doxycycline or clindamycin
  • Quinine plus doxycycline or clindamycin

Severe P.faciparum malaria

First-line alternatives

  • Artesunate  + amodiaquine
  • Artesunate  + sulfadoxine–pyrimethamine
  • Artemether–lumefantrine
  • Dihydroartemisinin plus piperaquine

Second-line alternatives

  • Artesunate plus doxycycline or clindamycin
  • Quinine plus doxycycline or clindamycin

Severe malaria due to P.ovale, P.vivax or P.malariae

First-line alternatives

  • Ceftriaxone, plus:
    • Artesunate and quinine
    • Artesunate plus sulfadoxine– pyrimethamine
    • Chloroquine combined with primaquine
    • ACTs combined with primaquine
    • No primaquine for P. malariae

Exchange blood transfusion for severe malaria

This is an extreme and inelegant form of therapy; you essentially remove all the parasite-rich blood, and replace with nice fresh parasite-free blood. Currently, there seems to be no agreement as to when one should resort to this, or how much blood to exchange.

Oh's Manual lists some indications:

  • Parasitaemia of over 30%
  • Parasitaemia of over 10% with organ system failure
  • Parasitaemia over 10% with failure to respond to vigorous drug therapy

However, there are vey few studies of this, and there does not seem to be a mortality benefit even in the small experimental studies.

A number of other unproven therapies are available to the desperate intensivist:

  • Monoclonal antibodies to TNF-α (shorten the duration of fever, but may worsen the CNS effects)
  • Curdlan sulfate (CS), a heparin-like sulfated 1 → 3-β-D glucan, can reduce the severity of the disease
  • Oral activated charcoal (improves cytokine storm)
  • Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, eg. rosiglitazone, may modulate the immune response, and appear to be safe
  • Anticoagulants (eg. heparin) to reduce the harmful cytoaggregation of red cells in the microcirculation
  • Iron chelators such as desferrioxamine, to reduce the organ damage from haemolysis and to restrict the availability of iron to the parasite 

Steroids and IV immunoglobulin have been demonstrated to worsen outcome.


Chapter 73  (pp. 743) Tropical  diseases  by Ramachandran  Sivakumar  and  Michael  E  Pelly

Santos, Lurdes C., et al. "Severe imported malaria in an intensive care unit: a review of 59 cases." Malar J 11.1 (2012): 96.

World Health Organization. Guidelines for the treatment of malaria. World Health Organization, 2006.

We dont have a CDC here in Australia, and so I link to the CDC site for details about standardised diagnosis and treatment of malaria. This page has links to downloadable PDF documents with decisionmaking flowcharts et cetera. One particularly useful document is this set of Guidelines for Clinicians.

Trampuz, Andrej, et al. "Clinical review: Severe malaria." CRITICAL CARE-LONDON- 7.4 (2003): 315-323.

WHO. Guidelines for the treatment of malaria. 2nd ed. Geneva: WHO; 2010. Online.

Marks, M., et al. "Managing malaria in the intensive care unit." British journal of anaesthesia 113.6 (2014): 910-921.

Kwiatkowski, D., et al. "Anti-TNF therapy inhibits fever in cerebral malaria." QJM: An International Journal of Medicine 86.2 (1993): 91-98.

Varo, Rosauro, et al. "Adjunctive therapy for severe malaria: a review and critical appraisal." Malaria journal 17.1 (2018): 1-18.