Viva 2

A 40-year-old previously well male is admitted to ICU for management of oliguric acute kidney injury accompanied by high fever with rigors, respiratory distress and headache. He has just returned from a brief tour of southeast Asia.

Give the most likely five differential diagnoses, and outline the features of the history and investigations that would help you distinguish between them.

(This viva dealt with the diagnosis and management of malaria.)

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)
  • Any reasonable differentials!
  • This could benefit from a "infectious/non-infectious" answer structure, but that could take too long. It's a febrile returned traveller, so the money is in the infectious diseases

History 

  • From the RACGP:
    • Travel history
    • Purpose and duration of travel
    • Drug history
    • Vaccination 
    • Exposure
      • Rural travel
      • Street food
      • Swimming in local fresh water, caves, game parks
      • Random unprotected sex
    • Duration of illness
    • Immune status

Investigations

  • Standard panel of biochemistry and bloods with focus on LFTs
  • Blood, urine, stool cultures
  • Thick and thin films
  • Arboviral and rickettsial serology
Prompt: what would you be looking for if you suspect malaria? What are the biochemical features you would expect with malaria?
  • hypoglycaemia
  • Haemoglobin in the urine
  • Deranged LFTs with raised bilirubin
  • DIC on coags
  • Thick and thin films
  • Rapid diagnostic tests (RDTs) looking for parasite antigens such as parasite-specific lactate dehydrogenase (pLDH), or aldolase.
Of the diagnostic tests which confirm malaria, what are the advantages and disadvantages for each?

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.
Malaria is confirmed by thick and thin films. P.falciparum is identified.
What are the features of severe malaria?
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
Prompt: what are the complications of severe malaria? What are the organ system effects?
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)
What specific management would you recommend?

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
What are the risk factors for death from malaria?
  • Young age (under 3)
  • Cerebral malaria
  • Organ system failure
  • Shock, circulatory collapse
  • Severe anaemia
  • High urea and lactate 
The patient continues to complain of headache, and his level of consciousness is deteriorating. What are your differentials?
  • Intracranial haemorrhage (eg. due to coagulopathy of DIC)
  • Cerebral malaria
  • Hepatic encephalopathy
  • Side effect of anti-malaria drugs
  • Postmalarial neurologic syndrome
What clinical features would you expect in cerebral malaria?
  • Symmetrical pyramidal signs
  • Retinal findings:
    • Retinal haemorrhages
    • Cotton wool spots
    • Papilloedema
    • Retinal whitening
    • Retinal vessel abnormalities
The patient's condition continues to deteriorate, and he develops multiorgan system dysfunction. What further management options are available?
  • Exchange transfusion is an option. 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

A number of 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.

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station. 

References

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.