Table 2.

Domains and risk of bias considered in risk of bias evaluation, according to Fowkes and Fulton [26]

Guideline	Checklist	Description
Is the study design appropriate to objectives?	objective common design	The type of study was marked in the appropriate \type of study. If the type of study was appropriate according to the study design was marked as “0” and as “++” if it was not appropriate.
	prevalence of Cross-sectional
	Prognosis Cohort
	Treatment Controlled trial
	Cohort, case-control, cross-sectional
Study sample representative?	Source of sample	It was identified as (0) when the origin was described in detail, a minor problem (+) when the study inaccurately cites the studied population region and a larger problem (++) was identified when the origin of the population was not mentioned sample.
	Sampling method	The item was assigned (0) for a full description of the sampling method, (+) for poor or no description of sample method, with no problem in matching between groups and (++) for poor or no description of sample method, interfering in the matching of the groups.
	Sample size	When the sample calculation was representative of the group, it was identified as (0). It was identified as a minor problem (+) when the sample calculation was not representative of the population under analysis, or when the study did not use a sample calculation. A larger problem (++) was identified when there was no sample calculation, and when the sample was < 50.
	Entry criteria/exclusion	The presence or absence of the points determined as important for eligibility in this review was assessed. The diagnosis of P. falciparum malaria, with groups with cerebral malaria and without cerebral malaria, was taken into account. Both sexes of all age groups were included, except pregnant women and participants identified with comorbidities and co-infected. For this criterion, it was identified as a minor problem (+) when two exclusion factors (pregnant women, comorbidities and co-infection) and a major problem (++) were present in the control group or the study group when two or more factors are present.
	Non-respondents	(0) was attributed to the studies that presented up to 30% positive responses by the population to participate in the studies, a minor problem (+) when there was a refusal, not being able to compromise the sample and a bigger problem (++) when there were refusal and commitment in sampling; in cross-sectional studies was assigned (NA)
Is the Control group acceptable?	Definition of controls	It was considered (0) studies that +showed control infected with P. falciparum, without cerebral malaria, a minor problem (++) when it was not clear the severity of the disease in the control group and a problem.
	Source of controls	It was identified as (0) when the origin was described in detail, a minor problem (+) when the study inaccurately cites the studied population region and a larger problem (++) was identified when the origin of the population was not mentioned sample.
	Matching/randomization	Studies with paired groups were considered a minor problem (+) in situations where it was not clear how the samples were paired, but the groups were paired with a larger problem (++) when there was no description or matching of sample groups.
	Comparable characteristics	We considered (0) studies that had sample groups with comparable characteristics and (++) when the study variables could not be matched and / or comparable.
Quality of measurements and outcomes?	Validity	(0) when the methods applied were appropriate for the study; was assigned a minor (+) problem when only one method for the analysis was used, but with reliable characteristics for the desired objective and a larger problem (++) when the methods used were not sufficient to meet the objective of the study.
	Reproducibility	(0) was identified when the evaluation of the methods was clearly described. They were considered as problems when the malaria diagnostic evaluation methods were not well described, do not describe how the sample was considered regarding the severity level of the disease, do not tell the type of infecting parasite, the lack of information regarding the quantification tests of TNF-α. A minor problem (+) when one of the previous items were present. A larger problem (++) when in presence two or more of the previous factors present.
	Blindness	It was considered (0) when the study presented blinding and (++) when it did not present blinding.
	Quality control	When the diagnosis of malaria was not performed by a health care provider, when analyzes of TNF-α levels were performed by academics in the absence of a supervisor or when it did not cite which professional performed the assessments, a minor problem (+) was considered when one of the previous items was present and a bigger problem (++) when two items were present in the studies.
Completeness	Compliance	It was considered (0) in the studies where the samples remained the same from the beginning to the end, or in a decreasing situation. There was no impairment in the power of the test used, (+) when the sample decrease during the study was able to compromise the. However, there were reasons and adjustments, and (++) was identified when the difference in sample size during the study compromised the power of the test, without justifiable reasons.
	Dropouts	It was considered as (0) when there was no withdrawal during the study, and (++) when there were withdrawals during the study; in cross-sectional studies was assigned Not Applicable (NA).
	Deaths	This item was scored as Not Applicable (NA) due to the type of PECO strategy.
	Missing data	The studies were identified with (0) when there was no loss of data (+) when there was loss without, however, compromising the statistical analysis and (++) when there was loss associated with the impairment of the statistical analysis.
Distorting influences?	Extraneous treatments	(0) was used when there was no influence of external factors, (+) when there were external factors without interfering in the results of the studies and (++) when there were external factors and impairment in the results
	Contamination	This item was scored as Not Applicable (NA) due to the type of PECO strategy.
	Changes over time	It was classified as NA because the studies were performed in a determined period after the diagnosis of P. falciparum infection.
	Confounding factors	It is characterized as a confounding factor when the patient of the study presents a clinical picture of previous anemia or when it presents a subclinical inflammatory picture. It was considered (0) when there were no confounding factors, a minor problem (+) when one of the factors was present, and a bigger problem (++) when two factors were present.
	Distortion reduced by analysis	(0) was used when in the studies are cited the adjustment of the variables that present distortions, (+) when the adjustment is cited in the studies, but it does not make clear the criteria used and (++) when the distortions were identified and not adjusted.
Summary questions	Bias: Are the results erroneously biased in a certain direction?	YES or “NO” answers were assigned for each question. If the answer is NO at the three questions, the article is considered reliable, with low risk of bias.
	Confounding: Are there any serious confusing or other distorting influences?
	Chance: Is it likely that the results occurred by chance?