We conclude that high numbers of transcriptionally active H. pylori are shed in vomitus, which indicates that new infections may be disseminated through vomiting.
We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was restored at convalescence. Immunoreactivity of vasoactive intestinal peptide (VIP) was increased during acute cholera, whereas in shigellosis VIP- and substance P-immunoreactive nerves appeared at early convalescence. Both shigellosis and cholera induced long-lasting degeneration of enteric neuronal axons, despite the presence of ongoing proliferation and regeneration processes. Neurotransmitters and neuropeptides may play differential roles in invasive and watery diarrhoea.
Background Vibrio cholerae, the causative agent of cholera, is responsible for significant morbidity and mortality worldwide. Children less than 5 years old have the highest disease burden of cholera in endemic areas. While children develop serum vibriocidal antibody responses to cholera vaccines, they derive less protection from vaccination compared with adults. The aim of our study was to determine whether the vibriocidal immune responses to V. cholerae infection are equally accurate as markers of protection in all age groups.MethodsCholera patients and their household contacts, who are known to be at high risk of V. cholerae infection, were enrolled between 2001 and 2017 in Dhaka, Bangladesh. Baseline vibriocidal titers were measured at the time of enrollment of household contacts, and participants were followed prospectively for development of V. cholerae infection.ResultsWe studied 50 contacts < 5 years old (“young children”), 228 contacts 5–16 years old (“older children”), and 548 contacts > 16 years old (“adults”). The baseline serum vibriocidal titer was higher in contacts who remained uninfected from all age groups than in contacts who developed cholera during the follow-up period (young children: P = 0.0092; older children: P = 0.0003, adults: P = 0.0012).ConclusionWe found that higher vibriocidal antibody titers were associated with protection against V. cholerae infection across all three age categories. These findings may help increase our understanding of the protective immune response against V. cholerae infection and have importance for future vaccine development strategies. Acknowledgments: This research was supported by Massachusetts General Hospital training grant T32AI007061.Disclosures All authors: No reported disclosures.
BackgroundCholera vaccines are recommended for use in outbreaks to prevent infections and reduce severity of disease. Variable immune responses are observed after administration of killed, whole-cell cholera vaccines, and limited data suggest that the gut microbiome may be one factor influencing immune responses to vaccination. Methods. We used microbial DNA sequencing of stool and serum vibriocidal titers to examine the gut microbiome and immune responses to vaccination at day 0, 7, 17 and 44 in adult vaccine recipients in Dhaka, Bangladesh. Using flow cytometry-based bacterial cell sorting, we identified IgA-coated gut microbes in stool before and after vaccination in a subset of patients. Results. Vibriocidal titer magnitude and kinetics were used to classify participants. Within 17 days of vaccination, 86/89 (96%) adults developed a four-fold rise in vibriocidal titer. Gut microbial diversity was not significantly changed after vaccination. Rate of seroconversion (four-fold increase in vibriocidal titer by Day 3 after vaccination) was faster in participants with increased bacteria from the genus Prevotella (multivariate analysis using linear models, q value 0.04). The gut microbes of participants with higher peak vibriocidal titers was characterized by increased Prevotella (3% vs. <0.1% of the total microbiome, P < 0.001 unpaired t-test, linear discriminant analysis score >3.5), particularly the species Prevotella copri (P < 0.001, unpaired t-test, linear discriminant analysis score >3.5). Lipopolysaccharide from Prevotella species is known to increase vaccination-associated antigen-specific antibody titers in animal models. Additionally, IgA coating of gut microbes in stool increased after vaccination, from 8.9% IgA coated at baseline to a peak level of 19% during follow-up (Wilcoxon signed rank test, P < 0.01). Conclusion. Certain microbiome profiles are correlated with greater immune responses to cholera vaccination, and IgA coating of gut bacteria indicates which commensal species may be participating in the mucosal immune response. The potential for modulation of mucosal immune responses based on gut microbial species warrants further study.Disclosures All authors: No reported disclosures.
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