Abstract
Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected). However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.
Highlights
Typhoid or enteric fever, caused primarily by Salmonella enterica subsp. enterica serovar Typhi
Hepatomegaly is encountered in approximately 30%-50% of typhoid patients with or without clinical manifestations [6,14], severe hepatic involvement concomitant with acute hepatitis is seen in 1-26% of typhoid fever patients [15] and the mortality rate due to typhoid hepatitis is reported to be between 20%-33% [16,17]
Despite the many complications that result from chronic carriage, the host and the bacterial contributions that create the environment that allows this chronic infection as a result of Salmonella infection and subsequent cancers are unknown
Summary
Typhoid or enteric fever, caused primarily by Salmonella enterica subsp. enterica serovar Typhi After ingestion through contaminated water or food, bacteria cross the intestinal epithelial barrier, migrate into the mesenteric lymph nodes, replicate in the reticulo-endothelial system and spread systemically producing significant inflammation and acute disease [2,3,4,5,6] with life-threatening complications including intestinal hemorrhage and perforation, septicemia and meningitis [7,8,9]. Hepatomegaly is encountered in approximately 30%-50% of typhoid patients with or without clinical manifestations [6,14], severe hepatic involvement concomitant with acute hepatitis is seen in 1-26% of typhoid fever patients [15] and the mortality rate due to typhoid hepatitis is reported to be between 20%-33% [16,17]
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