Plasmodium falciparum malaria and invasive bacterial co-infection in young African children: the dysfunctional spleen hypothesis

Children with recent or acute malaria episodes are at increased risk of invasive bacterial infections (IBI). However, the exact nature of the malaria-IBI association is still unclear. Young children have an age-related spleen immunologic immaturity, mainly due to the still ongoing development of the marginal zone (MZ) B cell subset. By mounting a rapid antibody response against encapsulated bacteria, these cells are critical for the defence against highly pathogenic microorganisms that do not elicit classical T cell-dependent responses. There is increasing evidence that the anatomy of the spleen becomes disorganized during malaria infection, with complete dissolution of the MZ and apoptosis of MZ B cells. Correspondingly, a reduction in the frequency of the peripheral equivalent of the MZ B cells has been found in malaria endemic areas. A remarkable similarity exists in IBI susceptibility between African children with malaria and hyposplenic or splenectomized patients. However, studies specifically assessing the immune function of the spleen in controlling bacterial infections in young children with malaria are scarce.