Malaria

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:

• Question 21.3 from the first paper of 2022
• Question 25 from the second paper of 2011
• Question 20  from the second paper of 2009
• Question 13 from the first paper of 2000

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.

Presentation

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 lactate (>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

Diagnosis

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

System	Complications
Respiratory	ARDS Pulmonary oedema
Circulatory	Shock, circulatory collapse Cardiac failure due to anaemia Haemorrhagic shock due to coagulopathy or splenic rupture
Neurological	Generalised weakness Decreased level of consciousness Increased ICP Seizures Hepatic encephalopathy
Endocrine	Hypoglycaemia Hyperkalemia Hyponatremia Acidosis (predominantly, lactic) Rhabomyolysis
Renal	Haemoglobinuria, leading to acute tubular necrosis Acute renal failure due to circulatory collapse ATN due to rhabdomyolysis
Gastrointestinal	Hepatosplenomegaly Splenic rupture Hepatic failure GI tract bleeding
Haematological	Disseminated intravascular coagulation Thrombocytopenia Haemolytic anaemia
Immunological	Hyperpyrexia (temperatures over 40°C)

Management

• 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)

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.