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8. Treatment of severe P. falciparum malaria

with signs of meningeal irritation (neck stiffness, photophobia or Kernig sign), but the
patient may be opistotonic. As untreated bacterial meningitis is almost invariably fatal, a
diagnostic lumbar puncture should be performed to exclude this condition. There is also
considerable clinical overlap between septicaemia, pneumonia and severe malaria – and
these conditions may coexist. In malaria endemic areas, particularly where parasitaemia
is common in the young age group, it is often impossible to rule out septicaemia in a
shocked or severely ill obtunded child. Where possible, blood should always be taken on
admission for culture and, if there is any doubt about the diagnosis, empirical antibiotic
treatment should be started immediately along with antimalarial treatment.

8.4 Specific antimalarial treatment

It is essential that effective, parenteral (or rectal) antimalarial treatment in full doses is
given promptly in severe malaria. Two classes of medicines are available for the parenteral
treatment of severe malaria: the cinchona alkaloids (quinine and quinidine) and the
artemisinin derivatives (artesunate, artemether and artemotil). Parenteral chloroquine
is no longer recommended for the treatment of severe malaria, because of widespread
resistance. Intramuscular sulfadoxine-pyrimethamine is also not recommended.

8.4.1 Artemisinin derivatives
Various artemisinin derivatives have been used in the treatment of severe malaria,
including artemether, artemisinin, artemotil and artesunate. Randomized trials
comparing artesunate and quinine from South-East Asia show clear evidence of benefit
with artesunate. In a multi-centre trial, which enrolled 1461 patients (including 202
children < 15 years old), mortality was reduced by 34.7% in the artesunate group when
compared to the quinine group. The results of this and smaller trials are consistent and
suggest that artesunate is the treatment of choice for adults with severe malaria.

Until recently there was insufficient evidence to make a similar recommendation in
children, from high transmission settings, so the guidelines for this important patient
group did not recommend artesunate above treatment with either artemether or quinine.
This has now changed with the publication of the AQUAMAT trial*, a multi-centre
study conducted in African children hospitalized with severe malaria. This very large
randomized controlled trial, which enrolled 5425 children < 15 years of age across
Africa, showed a significant mortality reduction by 22.5% in the artesunate group when
compared to the quinine group. The incidence of convulsions, coma, and hypoglycaemia
developing after hospital was also significantly reduced. Importantly there was no
significant difference in the incidence of severe neurological sequelae.

* Artesunate vs. quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open
-label randomized trial. Lancet 2010; 376: 1647–57
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