Gibani, Malick M, Jones, Elizabeth, Barton, Amber, Jin, Celina, Meek, Juliette, Camara, Susana, Galal, Ushma, Heinz, Eva, Rosenberg-Hasson, Yael, Obermoser, Gerlinde et al (show 17 more authors)
(2019)
Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model.
NATURE MEDICINE, 25 (7).
1082-+.
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Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model.pdf - Published version Download (7MB) | Preview |
Abstract
Salmonella Typhi is a human host-restricted pathogen that is responsible for typhoid fever in approximately 10.9 million people annually<sup>1</sup>. The typhoid toxin is postulated to have a central role in disease pathogenesis, the establishment of chronic infection and human host restriction<sup>2-6</sup>. However, its precise role in typhoid disease in humans is not fully defined. We studied the role of typhoid toxin in acute infection using a randomized, double-blind S. Typhi human challenge model<sup>7</sup>. Forty healthy volunteers were randomized (1:1) to oral challenge with 10<sup>4</sup> colony-forming units of wild-type or an isogenic typhoid toxin deletion mutant (TN) of S. Typhi. We observed no significant difference in the rate of typhoid infection (fever ≥38 °C for ≥12 h and/or S. Typhi bacteremia) between participants challenged with wild-type or TN S. Typhi (15 out of 21 (71%) versus 15 out of 19 (79%); P = 0.58). The duration of bacteremia was significantly longer in participants challenged with the TN strain compared with wild-type (47.6 hours (28.9-97.0) versus 30.3(3.6-49.4); P ≤ 0.001). The clinical syndrome was otherwise indistinguishable between wild-type and TN groups. These data suggest that the typhoid toxin is not required for infection and the development of early typhoid fever symptoms within the context of a human challenge model. Further clinical data are required to assess the role of typhoid toxin in severe disease or the establishment of bacterial carriage.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Animals, Mice, Inbred C57BL, Humans, Mice, Salmonella typhi, Typhoid Fever, Acute Disease, Bacterial Toxins, Double-Blind Method, Adolescent, Adult, Middle Aged, Young Adult |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Sep 2021 09:34 |
| Last Modified: | 18 Jan 2023 21:29 |
| DOI: | 10.1038/s41591-019-0505-4 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3136358 |
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