Cytokines have a systemic effect during the immune response of the host to malaria and are gaining popularity in the development of point-of-care diagnostics, not only for malaria but also for other inflammation-mediated diseases [
47,
48]. In this systematic review, differences of IL-5 levels between malaria and uninfected controls, and between severe and uncomplicated malaria were synthesized. The qualitative syntheses showed that the majority of included studies found no difference in IL-5 levels between malaria cases and uninfected controls [
24,
25,
27,
29,
30,
33,
35,
39‐
41,
43,
46]. These studies enrolled patients with
P. falciparum, except for the studies by Dobaño et al. [
29] and da Costa et al. [
45], which enrolled patients with
P. vivax malaria. These two studies were conducted in overlapping regions, but they enrolled different participants. Specifically, while Dobaño et al. [
29] enrolled pregnant women with asymptomatic malaria, da Costa et al. [
45] enrolled adults with uncomplicated malaria. There was homogeneity of the outcome of no difference in IL-5 levels between malaria cases and uninfected controls among the studies that enrolled children [
27,
40,
41,
43,
46]. Meanwhile, heterogeneity of IL-5 levels between malaria cases and uninfected controls was observed among pregnant women and adult participants [
24,
29,
33‐
35,
38,
39,
45]. Studies that enrolled pregnant women demonstrated no difference in IL-5 levels between malaria cases and uninfected controls, or showed that the former group had lower IL-5 levels [
29,
35,
38]. The heterogeneity of IL-5 levels among these studies may have been caused by the difference in the geographical distribution of
Plasmodium spp. or the method used for IL-5 measurement. In terms of the methods used to determine cytokine levels, Young et al. suggested that ELISA and bead-based assay yielded similar results for rat IFN-γ, TNF, and IL-6. ELISA was found to be more sensitive in the low range of the standard curve, whereas the bead assay could detect higher protein concentrations [
49]. Additionally, bead-based assays can be multiplex, enabling several cytokines to be detected in a platform [
50]. Nevertheless, the efficacy of these methods was not compared for IL-5. For this systematic review, 11 studies that used bead-based assays demonstrated homogeneous results of the IL-5 levels between malaria cases and uninfected controls [
24,
25,
27,
29,
33,
35,
39‐
41,
43,
46]. Meanwhile, heterogeneity of IL-5 levels was observed among studies that used ELISA for IL-5 measurement [
30,
38,
45].
The qualitative syntheses revealed that most studies found no difference in IL-5 levels between severe and non-severe malaria cases [
23‐
26]. Nonetheless, other studies demonstrated higher or lower IL-5 levels in patients with severe malaria than in those with uncomplicated malaria [
27,
42]. In terms of the particular complications, Armah et al. [
36] and Mandala et al. [
27] showed no difference in IL-5 levels between severe malarial anaemia and cerebral malaria, indicating that IL-5 levels were comparable in groups with complications of different severity. Nevertheless, Brickley et al. showed that IL-5 levels were significantly higher in children with severe anaemia than in those with non-severe anaemia [
37]. All of the aforementioned studies that evaluated the difference in IL-5 levels in patients with severe and uncomplicated malaria enrolled patients with
P. falciparum infection; as such, there was no heterogeneity of
Plasmodium spp. on the outcome of the synthesis analysis herein. Heterogeneity of IL-5 levels between severe malaria and uncomplicated malaria was observed with respect to geographical area. In Africa, IL-5 levels were either similar or higher in severe malaria cases relative to the levels in uncomplicated malaria [
23,
26,
27,
36,
37]. Meanwhile, in Asia similar or lower IL-5 levels were observed in severe malaria cases relative to uncomplicated malaria cases [
24,
25,
42]. Regarding the methods used for IL-5 measurement, studies that used bead-based assay showed either similar [
23‐
25] or higher [
27,
37] IL-5 levels in severe malaria than in uncomplicated malaria. Studies that used ELISA found similar [
26] or lower [
42] levels of IL-5 in severe malaria than in uncomplicated malaria.
This systematic review had some limitations. First, there were few studies investigating IL-5 in malaria, so the results of this review were limited. Second, the meta-analysis to pool the mean difference in IL-5 levels among severe malaria, uncomplicated malaria, and uninfected controls could not be performed due to the few studies reporting quantitative data for IL-5 levels between groups of participants.