The Impact of Vaccination and Prior Exposure on Stool Shedding of Salmonella Typhi and Salmonella Paratyphi in 6 Controlled Human Infection Studies


Gibani, Malick M, Voysey, Merryn, Jin, Celina, Jones, Claire, Thomaides-Brears, Helena, Jones, Elizabeth, Baker, Philip, Morgan, Marcus, Simmons, Alison, Gordon, Melita A ORCID: 0000-0002-0629-0884 et al (show 6 more authors) (2019) The Impact of Vaccination and Prior Exposure on Stool Shedding of Salmonella Typhi and Salmonella Paratyphi in 6 Controlled Human Infection Studies. CLINICAL INFECTIOUS DISEASES, 68 (08). pp. 1265-1273.

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Abstract

Background: Shedding of Salmonella Typhi or Paratyphi in the stool or urine leads to contamination of food or water, which is a prerequisite for transmission of enteric fever. Currently, there are limited data on the effect of vaccination or prior exposure on stool shedding. Methods: Six Salmonella Typhi or Paratyphi human challenge studies were conducted between 2011 and 2017. Participants were either unvaccinated or vaccinated with 1 of 4 vaccines: Vi-polysaccharide (Vi-PS), Vi-tetanus-toxoid conjugate vaccine (Vi-TT), live oral Ty21a vaccine, or an experimental vaccine (M01ZH09). Daily stool cultures were collected for 14 days after challenge. Results:There were 4934 stool samples collected from 430 volunteers. Participants who received Vi-PS or Vi-TT shed less than unvaccinated participants (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.15–0.77; P = .010 and OR, 0.41; 95% CI, 0.19–0.91, P = .029 for Vi-PS and Vi-TT, respectively). Higher anti-Vi immunoglobulin G titers were associated with less shedding of S. Typhi (P < .0001). A nonsignificant reduction in shedding was associated with Ty21a vaccine (OR, 0.57; 95% CI, 0.27–1.20; P = .140). Individuals previously exposed to S. Typhi shed less than previously unexposed individuals (OR, 0.30; 95% CI, 0.1–0.8; P = .016). Shedding of S. Typhi was more common than S. Paratyphi. Conclusions: Prior vaccination with Vi vaccines, or natural infection, reduces onward transmission of S. Typhi. Field trials of Vi-TT should be designed to detect indirect protection, reflecting the consequence of reduced stool shedding observed in the human challenge model.

Item Type: Article
Uncontrolled Keywords: stool shedding, Salmonella Typhi, indirect effects, typhoid conjugate vaccine, Vi-polysaccharide vaccine
Depositing User: Symplectic Admin
Date Deposited: 12 Feb 2019 11:52
Last Modified: 19 Jan 2023 01:14
DOI: 10.1093/cid/ciy670
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3027395
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