Naing, Cho Min, Ni, Han, Basavaraj, Arun Kumar, Aung, Htar Htar, Tung, Wong Siew, and Whittaker, Maxine A. (2024) Cytokine levels in the severity of falciparum malaria: An umbrella review. Acta Tropica, 260. 107447.

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Abstract

This study aimed to synthesise evidence comparing the levels of cytokines in severe falciparum malaria with those in uncomplicated malaria from available systematic reviews and meta- analyses. Relevant individual meta-analyses were searched in PubMed, Ovid, and Google Scholar, following the selection criteria specified for this umbrella review. The AMSTAR-2 tool was applied to grade the quality of the meta-analyses identified. The random-effects model was applied to recalculate the effect sizes of each included meta-analysis. Heterogeneity between meta-analyses was investigated with I2 value. 95% predicting interval (PI) for the summary random-effects model was also made. In each meta-analysis identified, information on largest study’s effect, the excess significance test, small study effects, and publication bias were addressed. This umbrella review included nine meta-analyses (n = 12,674) for nine unique cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, and TNF-α). Only one individual meta-analysis showed significantly higher levels of cytokine IL-1β (p: 0.009) amongst those with severe falciparum malaria compared to those with uncomplicated malaria. The 95% PIs did not show significance in any individual meta-analyses. Nine individual meta-analyses showed substantial heterogeneity, with I2 tests ranging from 81% to 99%. Two independent meta-analyses (the IL-4 and IL-12) showed evidence of ‘excess significant bias’. The meta-analysis of IL-1β only showed “Class III evidence”, indicating that this cytokine was “suggestive” in contributing to those with severity of malaria in comparison to those with uncomplicated malaria. The remaining eight cytokines showed “Class IV evidence,” indicating "weak" evidence on the impact of malaria severity.

In conclusion, the findings suggest that compared to uncomplicated malaria, pro-inflammatory cytokine IL-1β contributes to the development of severe falciparum malaria. Due to the limited level of evidence, further well-designed larger studies with multiple cytokines are needed to investigate cytokine levels as reliable biomarkers in malaria severity.

Item ID:	84878
Item Type:	Article (Research - C1)
ISSN:	1873-6254
Copyright Information:	© 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Date Deposited:	13 Mar 2025 01:14
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics) @ 50% 42 HEALTH SCIENCES > 4203 Health services and systems > 420310 Health surveillance @ 50%
SEO Codes:	20 HEALTH > 2004 Public health (excl. specific population health) > 200499 Public health (excl. specific population health) not elsewhere classified @ 100%
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