How to treat severe malaria

Learn how to treat and manage severe malaria in your patients from an expert in this Medmastery article.
Last update29th Apr 2021

Patients with severe malaria should be treated aggressively with intravenous therapy (IV) anti-malarials. But first, let’s take a closer look at what severe malaria looks like, and how we manage patients with severe malaria.

What is severe malaria?

We classify Plasmodium falciparum infection as severe malaria when a positive diagnostic test for malaria is accompanied by the presence of at least one of a number of clinical criteria:

  1. Impaired consciousness or coma
  2. Severe anemia (hemoglobin < 7g / dL)
  3. Acute kidney injury
  4. Acute respiratory distress syndrome (ARDS)
  5. Disseminated intravascular coagulation (DIC)
  6. Spontaneous bleeding
  7. Acidosis
  8. Jaundice
  9. More than 5% of red blood cells (RBCs) on a blood film are infected
Figure 1. Clinical features of severe malaria in adults include impaired consciousness, severe anemia, acute kidney injury, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), spontaneous bleeding, acidosis, jaundice, and high parasite load when more than 5% of red blood cells (RBCs) on a blood film are infected.

What anti-malaria drugs should I use to treat severe malaria?

When treating severe malaria, obviously we first want to get rid of the cause—the parasite—using anti-malaria drugs.

Historically, for severe malaria, we used quinidine, an anti-arrhythmic related to quinine. However, recent studies have shown that the anti-malarial drug, artesunate, results in much lower mortality than quinidine when used to treat severe malaria, so it has become the standard treatment over quinidine.

Artesunate, given intravenously, works by disrupting the mitochondrial membrane and the energy production of the mitochondrion, causing the parasite to die.

Figure 2. Artesunate disrupts the mitochondrial membrane and mitochondrial energy production which kills Plasmodium falciparum parasites.

Artesunate can also be used in patients with less severe malaria who cannot take quinine-based medications.

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How should I address the other symptoms that are associated with severe malaria?

So, we’ve addressed treatment to eliminate the parasite. But remember that a patient may already be quite sick, so we’ll likely also need to treat their symptoms.

A patient may need mechanical ventilation, benzodiazepines for controlling seizures, or fluids for the accompanying DIC.

In very severe cases, exchange transfusions may help to get rid of the blood containing the high-grade parasitemia by replacing it with some uninfected blood. This technique has been life-saving in a few individuals.

Although coinfection is uncommon, keep in mind that patients with severe malaria can have two infections going on simultaneously. So, it’s prudent to draw blood cultures to check for other infections.

Finally, if the patient has severe malaria and the neurological presentation is the least bit atypical, consider a lumbar puncture to test the cerebrospinal fluid for infection. For instance, cerebral malaria is generally associated with increased intracranial pressure, but not with neck stiffness. So a patient complaining of neck stiffness suggests meningitis and warrants a lumbar puncture to rule out other causes of central nervous system (CNS) infections.

Figure 3. When treating severe malaria, in addition to administering antimalarials, other actions to manage symptoms and rule out infections may include the use of benzodiazepines, intravenous (IV) fluids, mechanical ventilation, exchange transfusion, blood cultures, and lumbar punctures.

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Recommended readings

  • Ashley, EA, Phyo, AP, and Woodrow, CJ. 2018. Malaria. Lancet391: 1608­–1621. PMID: 29631781
  • Fairhurst, RM and Wellems, TE. 2014. “Malaria (Plasmodium Species)”. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Bennett, JE, Dolin, R, Blaser, MJ. 8th edition. Philadelphia: Elsevier Saunders. (Fairhurst and Wellems 2014, 3070–3090)
  • Phillips, MA, Burrows, JN, Manyando, C, et al. 2017. Malaria. Nat Rev Dis Primers3: 17050. PMID: 28770814
  • World Health Organization. 2015. Guidelines for treatment of malaria third edition. World Health OrganizationWorld Health Organization
  • World Health Organization. 2019. World malaria report 2019. World Health Organizationhttps://www.who.int

About the author

John F. Fisher, MD MACP FIDSA
Professor of Medicine (Infectious Diseases) at the Medical College of Georgia, Augusta University, USA.
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