Question 20

College Answer

The clinical features include:
History of recent travel to a malaria endemic zone
Impaired conscious state
Convulsions
Respiratory distress and ARDS

Shock and circulatory collapse

Jaundice
Severe hemoglobinuria
Severe anaemia

Treatment:
Two classes of drugs are available: Cinchona alkaloids and the artemisinin derivatives (latter may be superior in adults). Initially commenced as parenteral and switched to oral for a total of 7 days. Doxycycline is added to non-pregnant adults. If pregnant, then clindamycin is given in addition.

Supportive therapy of organ dysfunction

Specific other treatments:
a) No proven role for exchange transfusion in severe parasitemia, although used

b) risk of hypoglycemia with quinine

Discussion

Malaria in general is briefly summarised in the Required Reading section.

What the hell is "severe" malaria? The WHO in an excellent summary statement (2000) have suggested the following definition:

• Prostration
• Decreased level of consciousness
• Respiratory distress
• Pulmonary oedema
• Seziures
• Circulatory collapse
• Coagulopathy
• Jaundice
• Haemoglobinuria
• Severe anaemia

One can see that it closely resembles the college answer.

Furthermore, one wonders as to how a history of travel is a clinical feature.

Staying in the trend of using WHO recommendations for this answer, a 2010 guidelines statementsuggests the following management strategy for severe falciparum malaria:

• Artemisinin derivatives are first line: IV artesunate "significantly reduced the risk of death compared to quinine" in the AQUAMAT trial; previously to 2010 the guidelines did nto have enough evidence to recommend artsunate over quinine.
• Quinine is second-line, and the WHO reluctantly recommends it while reminding us that its position as a malaria treatment "was established before modern clinical trial methods were developed".
• Doxycycline is recommended as a part f the "follow-on" treatment, when the intial critical illness settles and the patient can tolerate oral therapy. As always with tertracyclines, it is to be avoided in pregnancy or lactation.

As for exchange transfusion - it does not seem to improve survival, but the authors of the 2002 meta-analysis confess that there are no randomised controlled trials, and that the comparative cohort studies they reviewed had "significant problems with the comparability of treatment groups".

World Health Organization. "Severe falciparum malaria." Transactions of the Royal Society of Tropical Medicine and Hygiene 94 (2000): 1-90.

Riddle, Mark S., et al. "Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis." Clinical infectious diseases34.9 (2002): 1192-1198.

Reyburn, Hugh. "New WHO guidelines for the treatment of malaria." BMJ 340 (2010).

(the actual revised guidelines are available online for free)

Dondorp, Arjen M., et al. "Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial." The Lancet 376.9753 (2010): 1647-1657.

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