Rickettsia felis causes flea-borne spotted fever (FBSF), an acute febrile illness commonly involving headache, myalgia and rash and potentially leading to severe neurological and respiratory complications [
1]. While distributed worldwide,
R. felis infection is increasingly reported in Africa, where prevalence rates of 3–15% in acute fever episodes suggest an emerging importance as a cause of febrile illness [
2‐
5]. The obligate intracellular pathogen
R. felis belongs to the transitional group of rickettsiae, as it shares phenotypic characteristics with members of the spotted fever group (SFG) and the typhus group (TG) [
2]. Rickettsiae cause endothelial cell (EC) infection which can lead to vasculitis and bacterial dissemination [
6]. The vascular permeability observed in clinical cases seems to be mediated at least in part by inflammatory cells and their mediators [
7]. ECs, that are besides macrophages the major target cells for rickettsial infections [
8‐
12], react to infection with TG and SFG rickettsia with the production of proinflammatory cytokines like IL-1 (interleukin-1), IL-6 and TNFα (tumor necrosis factor-α), chemokines like IL-8, IP-10 (interferon-γ induced protein-10) and MCP-1 (monocyte chemotactic protein-1) and other mediators in vitro that lead to activation and recruitment of immune cells to the site of infection [
8,
13‐
17]. IL-8, for example, promotes the recruitment of neutrophils to the site of infection and mediates angiogenesis [
18‐
20]. IP-10 and MCP-1 are involved in the recruitment of monocytes and activated NK cells and T cells which further lead to potentiation of the inflammatory response to rickettsial infection and its clearance [
21‐
23]. Mouse models of rickettsial infections further help to understand the role of cytokines in vivo. IFNγ (interferon-γ) and TNFα have protective properties during rickettsial infection of susceptible mouse strains [
24‐
29]. IFNγ and TNFα activate intracellular bactericidal mechanisms; it was shown that IFNγ inhibits the growth of rickettsia in various host cells [
28‐
33]. However, in humans, the early host immune responses have not been well-characterized. In this study, we investigated serum cytokine responses in febrile children from Ghana with acute
R. felis infection.