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Association of cerebral malaria and TNF-α levels: a systematic review
Luana Leão1, Bruna Puty1, Maria Fâni Dolabela2
1Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, 01 Augusto Correa Street, Guama, Belem, PA, 66075-900, Brazil.
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-α 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-α 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- α plasma dosage, while two have evaluated at the blood and one at the brain (post-Morten). Among them, only five studies showed higher TNF-α 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-α level is associated with cerebral malaria, the evidence is inconsistent and imprecise. More observational studies evaluating the average TNF-alpha are needed.
Insights
Tumor necrosis factor-alpha (TNF-α) levels may be linked to cerebral malaria, the most severe Plasmodium falciparum infection. However, current evidence is inconsistent, requiring more research on TNF-α in cerebral malaria.
Area of Science:
- Infectious Diseases
- Immunology
- Neuroscience
Background:
- Cerebral malaria, a severe Plasmodium falciparum infection, involves a significant inflammatory response.
- Tumor necrosis factor-alpha (TNF-α) is a key inflammatory cytokine implicated in malaria pathogenesis.
Purpose of the Study:
- To systematically review the association between TNF-α levels and cerebral malaria.
- To synthesize existing evidence on TNF-α in Plasmodium falciparum infections.
Main Methods:
- Systematic review adhering to PRISMA guidelines.
- Comprehensive literature search across major databases (PubMed, LILACS, Scopus, Web of Science, Cochrane, OpenGrey, Google Scholar).
- Inclusion of studies on human P. falciparum infection with or without cerebral malaria and TNF-α dosage, assessed using risk of bias and GRADE tools.
Main Results:
- Eight articles were eligible from 2338 initially identified studies.
- Five studies indicated higher TNF-α levels in cerebral malaria patients compared to severe malaria.
- Varied sample types (plasma, blood, brain tissue) and methodological limitations (sample size, randomization) were noted.
Conclusions:
- The association between TNF-α levels and cerebral malaria is suggested but lacks consistent and precise evidence.
- Further observational studies are necessary to clarify the role of TNF-α in cerebral malaria.
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