Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis

Abstract

In sub-Saharan Africa, chronic hepatosplenomegaly, with palpable firm/hard organ consistency, is common, particularly among school-aged children. This morbidity can be caused by long-term exposure to malaria, or by Schistosoma mansoni, and it is exacerbated when these two occur together. Although immunological mechanisms probably underlie the pathogenic process, these mechanisms have not been identified, nor is it known whether the two parasites augment the same mechanisms or induce unrelated processes that nonetheless have additive or synergistic effects. Kenyan primary schoolchildren, living in a malaria/schistosomiasis co-transmission area, participated in cross-sectional parasitological and clinical studies in which circulating immune modulator levels were also measured. Plasma IL-12p70, sTNF-RII, IL-10 and IL-13 levels correlated with relative exposure to malaria, and with hepatosplenomegaly. Soluble-TNF-RII and IL-10 were higher in children infected with S. mansoni. Hepatosplenomegaly caused by chronic exposure to malaria was clearly associated with increased circulating levels of pro-inflammatory mediators, with higher levels of regulatory modulators, and with tissue repair cytokines, perhaps being required to control the inflammatory response. The higher levels of regulatory modulators amongst S. mansoni infected children, compared to those without detectable S. mansoni and malarial infections, but exposed to malaria, suggest that S. mansoni infection may augment the underlying inflammatory reaction.

Figure 1

Levels of circulating immune mediators by clinical groupings of organomegaly. Shown are the levels of cytokines which were significantly different between clinical groupings of organomegaly: neither liver nor spleen enlargement, S, spleen enlargement; H, liver enlargement; HS, hepatosplenomegaly. Outliers were removed. *Significantly different from children with hepatosplenomegaly. +Significantly different from children with spleen enlargement. $Significantly different from children with liver enlargement. $/*/+P < 0·05, **/++ < 0·001, ***/+++P < 0·001.

Figure 2

Levels of circulating immune mediators by extent of liver enlargement. Shown are the levels of cytokines that were significantly different between groups representing differing extents of liver enlargement. Outliers were removed. *Significantly different from children with substantial spleen enlargement (> 5 cm). +Significantly different from children with moderate spleen enlargement (3–5 cm). */+P < 0·05, **/++P < 0·001, ***/+++P < 0·001.

Figure 3

Levels of circulating immune mediators by extent of spleen enlargement. Shown are the levels of cytokines that were significantly different between groups representing differing extents of spleen enlargement. Outliers were removed. *Significantly different from children with substantial spleen enlargement (> 4 cm). +Significantly different from children with moderate spleen enlargement (3–4 cm). */+P < 0·05, **/++P < 0·001, ***/+++P < 0·001.