Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?

Abstract

Non-typhoidal Salmonella usually induces self-limiting gastroenteritis. However, in many parts of Africa, especially in individuals who are malnourished, infected with malaria, or have sickle cell disease, the organism causes serious and potentially fatal systemic infections. Since the portal of entry of non-typhoidal Salmonella into the systemic circulation is by way of the intestine, we argue that an increased gut permeability plays a vital role in the initiation of invasive non-typhoidal Salmonella in these patients. Here, we will appraise the evidence supporting a breach in the intestinal barrier and propose the mechanisms for the increased risks for invasive non-typhoidal Salmonella infections in these individuals.

High genetic similarity between non-typhoidal Salmonella isolated from paired blood and stool samples of children in the Democratic Republic of the Congo

“…This "typhoid fever-like" scenario would be in line with the clinical presentation of invasive NTS infections in sSA, i.e. febrile systemic fever with non-specific clinical features, without gastroenteritis [13] but with increased gut permeability driven by Plasmodium falciparum sequestration and altered gut microbiota associated with malnutrition [42,43].…”

“…e . febrile systemic fever with non-specific clinical features, without gastroenteritis [ 13 ] but with increased gut permeability driven by Plasmodium falciparum sequestration and altered gut microbiota associated with malnutrition [ 42 , 43 ].…”

Salmonella Virulence and Immune Escape

“…iNTS disease is caused mainly by S. Typhimurium, S. Enteritidis, and S. Dublin [8]. The iNTS disease burden in Africa is especially caused due to urbanization with large populations living in crowded and insanitary conditions with poor access to potable water [62][63][64]. iNTS is more common amongst people with an impaired immunity, and typically represents a febrile systemic illness and lower respiratory tract disease, commonly attributable to co-infections with HIV or malaria [50,60,65,66].…”

Undernutrition: a major but potentially preventable cause of poor outcomes in children living with sickle cell disease in Africa

“…In addition, as for all organ systems, the gut can be damaged in children with sickle cell disease through vasculopathic processes that include recurrent hypoxiareperfusion injury induced by vaso-occlusive crises (VOC), which could also lead to reduced nutrient absorptive capacity. Recent studies suggest that VOCs initiate a cascade of interconnected changes in the gut that include enterocyte injury and apoptosis, local inflammation and immune activation, disruption of tight junction integrity, and an altered population and function of gut microbiota [8,9]. On the background of this pathophysiological complexity, the analysis by Islam, which reported that the association of SCD with anthropometric indices was significantly and strongly mediated by haemoglobin levels, should be interpreted with some caution [5].…”