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

Abstract

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.Here, it is hypothesized that Plasmodium falciparum malaria infection constitutes a detrimental factor in the still immature spleen function of young children, resulting in a factually hyposplenic state during malaria episodes, putting children with malaria at a high risk to develop life-threatening bacterial infections. Studies to confirm or reject this hypothesis are greatly needed, as well as the development of affordable and feasible tools to assess the immune spleen function against encapsulated bacteria in children with malaria.

Vivax infection alters peripheral B‐cell profile and induces persistent serum IgM

“…However, apoptosis of MZ B cells has been observed in infection with P. chaubaudi in the murine model . MZ B cells have also been shown to undergo apoptosis with a consequent decrease in numbers in the blood of patients suffering from repeated falciparum infections . The role of these cells in acute vivax infection, especially in hypoendemic areas, needs to be investigated.…”

The potential impact of coinfection on antimicrobial chemotherapy and drug resistance

“…In humans, measles infection can considerably suppress the immune system, thereby increasing the pathogenicity of coinfecting microbes [19, 100]. Similarly, malaria infections in young children are associated with an increased risk of invasive bacterial infections, possibly through malaria-induced spleen dysfunction [20]. Lastly, epithelial cell damage and/or dysfunctional innate immune responses triggered by influenza infections may cause a transiently elevated incidence of bacterial coinfections [12,21].…”

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children

“…Furthermore, P. falciparum infection may compromise humoral immunity to NTS via a reduction of the antibody opsonization capacity as observed in some studies (32), as well as via defective complement cascade activation. This observation suggests that in children in settings where exposure to NTS is frequent and where malaria is highly endemic, humoral bactericidal immunity may be lost during repeated malaria episodes, increasing overall susceptibility to iNTS by favoring NTS proliferation and systemic infection.…”