Abstract
BackgroundThe Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap.MethodsCirculating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA.ResultsThe results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon.ConclusionsTaken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.
Highlights
The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups
There were no differences in age, haemoglobin levels and axillary temperature between the Dogon and Fulani children groups, irrespective of infectious status (Table 1)
There were two outliers among the infected Fulani children with very high parasitaemia. When these were excluded from the analysis the mean parasite density in Fulani was 1,618 (100-7,875) asexual parasites/μl and being less parasitized compared to Dogon (p = 0.004)
Summary
The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. Other pro-inflammatory cytokines such as interleukin (IL)-12 and tumour necrosis factor (TNF) have shown to be essential mediators in this protection [4]. They all appear to be necessary for the inhibition of parasite growth and stimulation of phagocytosis to enhance clearance of parasitized erythrocytes. Plasma levels of TNF and nitric oxide, secreted by activated macrophages and neutrophils, are associated with resolution of fever and parasite clearance [3] Other cytokines such as IL-1, IL-6, IL-8, IL-10 and IL-12 have been implicated in the pathogenesis of severe malaria cases compared to uncomplicated and matched healthy controls [5,6]
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