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Adjunctive therapy for severe malaria: a review and critical appraisal
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BACKGROUND: Despite recent efforts and successes in reducing
the malaria burden globally, this infection still accounts for
an estimated 212 million clinical cases, 2 million severe
malaria cases, and approximately 429,000 deaths annually. Even
with the routine use of effective anti-malarial drugs, the case
fatality rate for severe malaria remains unacceptably high, with
cerebral malaria being one of the most life-threatening
complications. Up to one-third of cerebral malaria survivors are
left with long-term cognitive and neurological deficits. From a
population point of view, the decrease of malaria transmission
may jeopardize the development of naturally acquired immunity
against the infection, leading to fewer total cases, but
potentially an increase in severe cases. The pathophysiology of
severe and cerebral malaria is not completely understood, but
both parasite and host determinants contribute to its onset and
outcomes. Adjunctive therapy, based on modulating the host
response to infection, could help to improve the outcomes
achieved with specific anti-malarial therapy. RESULTS AND
CONCLUSIONS: In the last decades, several interventions
targeting different pathways have been tested. However, none of
these strategies have demonstrated clear beneficial effects, and
some have shown deleterious outcomes. This review aims to
summarize evidence from clinical trials testing different
adjunctive therapy for severe and cerebral malaria in humans. It
also highlights some preclinical studies which have evaluated
novel strategies and other candidate therapeutics that may be
evaluated in future clinical trials.
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VARO, Rosauro, et al. Adjunctive therapy for severe malaria: a review and critical
appraisal. Malaria Journal. 2018. Vol. 17, num. 47. ISSN 1475-2875. [consulted: 9 of June of 2026]. Available at: https://hdl.handle.net/2445/134541