The Microbiological and Clinical Characteristics of Invasive Salmonella in Gallbladders from Cholecystectomy Patients in Kathmandu, Nepal

Abstract

Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination.

Carriage prevalence of Salmonella enterica serotype Typhi in gallbladders of adult autopsy cases from Mozambique

“…It has been demonstrated that Salmonella reaches the gallbladder and replicates within the epithelial cells of this tissue, provoking epithelial destruction and local neutrophil infiltrate [11]. This high carrier incidence is remarkable compared with the low frequency of S. Typhi recovered from blood cultures of children < 15 years in Manhiça district, a rural area 80 km of Maputo, where the autopsies were performed.…”

“…A study carried out in Chile reported a prevalence of 11.2% of S. Typhi carriers in gallbladder samples collected after surgery for gallbladder infection [6]. In Kathmandu, Nepal, Dongol et al [11] found a prevalence of S. Typhi carriers of 1.7% on analyzing bile samples from cholecystectomy patients. Gonzalez-Escobedo et al [9] found that only 5% (5/103) of patients with cholelithiosis presented S. Typhi.…”

What's on the Outside Matters: The Role of the Extracellular Polymeric Substance of Gram-negative Biofilms in Evading Host Immunity and as a Target for Therapeutic Intervention

“…Gallbladder colonization by Salmonella during chronic infection has been known for more than a century. A high percentage of human carriers harbor gallstones, and biofilms form on gallstone surfaces during chronic carriage (64,65). A mouse model of carriage has been developed based on the documented long-term survival of St (the mouse model for the human-specific Sty) in NRAMP1 ϩ/ϩ (SLC11A1) mice (129X1/SvJ) and the ability to induce gallstone formation in the mouse with a lithogenic diet (66).…”

Gallbladder Epithelium as a Niche for Chronic Salmonella Carriage

“…These carriers serve as a critical reservoir for further spread of the disease through bacterial shedding in feces (5). Chronic infections can persist for decades, and although highly contagious, they are typically asymptomatic (6)(7)(8). In addition, chronic carriers have an approximately 8-fold greater risk of developing gallbladder carcinoma than noncarriers (9,10).…”

“…They are typically encased in an extracellular matrix and are associated with many chronic and acute human infections (12,13). The carrier state is highly related to the presence of gallstones (6,14,15). Indeed, studies in our laboratory have shown that Salmonella can form biofilms on the surface of cholesterol gallstones in vitro and in vivo in the gallbladder of mice and human carriers (16,17).…”