A plausible explanation for male dominance in typhoid ileal perforation

Abstract

The phenomenon of consistent male dominance in typhoid ileal perforation (TIP) is not well understood. It cannot be explained on the basis of microbial virulence, Peyer’s patch anatomy, ileal wall thickness, gastric acidity, host genetic factors, or sex-linked bias in hospital attendance. The cytokine response to an intestinal infection in males is predominantly proinflammatory as compared with that in females, presumably due to differences in the sex hormonal milieu. Sex hormone receptors have been detected on lymphocytes and macrophages, including on Peyer’s patches, inflammation of which (probably similar to the Shwartzman reaction/Koch phenomenon) is the forerunner of TIP, and is not excluded from the regulatory effects of sex hormones. Hormonal control of host-pathogen interaction may override genetic control. Environmental exposure to Salmonella typhi may be more frequent in males, presumably due to sex-linked differences in hygiene practices and dining-out behavior. A plausible explanation of male dominance in TIP could include sex-linked differences in the degree of natural exposure of Peyer’s patches to S. typhi. An alternative explanation may include sexual dimorphism in host inflammatory response patterns in Peyer’s patches that have been induced by S. typhi. Both hypotheses are testable.

Enteric Fever Complicated by Intestinal Perforation in Children: A Persistent Health Problem Requiring Surgical Management

“…However, Khan M et al proposed that genetic and host inflammatory response also play a role. 8 High grade fever followed by abdominal pain was the most consistent feature as also seen in various studies. 5 Three patients presented with psychosis.…”

Antibiotic Susceptibility Patterns of Salmonella Typhi and Salmonella Paratyphi in a Tertiary Care Hospital in Islamabad

“…Other studies also reported a similar gender distribution [1,13,16,17]. Plausible explanation for this male predominance is the fact that males have more outdoor exposure and are more likely to consume street foods as compared to females in Pakistani society [1,13,17]. Street food consumption is an important risk factor for enteric fever [18].…”

Sexual dimorphism in bacterial infections

“…Certain gastrointestinal infections are more recurrent and severe in men than in women. This sexual dimorphism can be explained in part because of behavioral differences during hygiene and eating practices, such as handwashing before food handling and eating, storage, refrigeration, and defrosting practices, and tendency of men to eat undercooked or raw food, as well as to ingest roadside food [ 30 ]. Although sexual dimorphism in gastrointestinal infections is mainly due to immune differences, these differences in turn can be influenced by the above mentioned behavioral dissimilarities between women and men.…”

“…Although sexual dimorphism in gastrointestinal infections is mainly due to immune differences, these differences in turn can be influenced by the above mentioned behavioral dissimilarities between women and men. This is the case of typhoid fever and its complication: typhoid ileal perforation (TIP) [ 30 ]. TIP is characterized by an exacerbated inflammatory activity at Peyer’s patches, probably in response to Salmonella typhi exposure and re-exposure events due to behavioral factors that favors infection in men.…”

“…During gastrointestinal injury, males produce predominantly pro-inflammatory cytokines, such as IL-6 and TNF-α, as compared with females whose intestine produce anti-inflammatory factors such as IL-10 as well as protective factors of endothelial function such as a modest rise in nitric oxide (NO) levels [ 31 ]; in turn, the inflammatory response in males leads to perforation and cell necrosis at the site of infection [ 30 ]. Sex hormones signaling through their cognate receptors could play an important role in the progression of this pathology and their low incidence in women since both isoforms of ER (ER-α and ER-β) have been identified at Peyer’s patches [ 30 , 32 ], and estradiol induces T cell proliferation and activity, as well as production of anti-inflammatory cytokines [ 32 ]. The differential concentrations of sex hormones between men and women influence the type of immune response that is activated.…”