Background: Cerebral malaria is the most severe form of infection with Plasmodium falciparum characterized by a
highly inflammatory response. This systematic review aimed to investigate the association between TNF-? levels
and cerebral malaria.
Methods: This review followed the Preferred Reporting of Systematic Review and Meta-analyses (PRISMA)
guidelines. The search was performed at PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey
and Google Scholar. We have included studies of P. falciparum-infected humans with or without cerebral malaria
and TNF-? dosage level. All studies were evaluated using a risk of bias tool and the GRADE approach.
Results: Our results have identified 2338 studies, and 8 articles were eligible according to this systematic review
inclusion criteria. Among the eight articles, five have evaluated TNF- ? plasma dosage, while two have evaluated at
the blood and one at the brain (post-Morten). Among them, only five studies showed higher TNF-? levels in the
cerebral malaria group compared to the severe malaria group. Methodological problems were identified regarding
sample size, randomization and blindness, but no risk of bias was detected.
Conclusion: Although the results suggested that that TNF-? level is associated with cerebral malaria, the evidence
is inconsistent and imprecise. More observational studies evaluating the average TNF-alpha are needed.
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