| Title: |
Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model. |
| Authors: |
Gibani, Malick M; Jones, Elizabeth; Barton, Amber; Jin, Celina; Meek, Juliette; Camara, Susana; Galal, Ushma; Heinz, Eva; Rosenberg-Hasson, Yael; Obermoser, Gerlinde; Jones, Claire; Campbell, Danielle; Black, Charlotte; Thomaides-Brears, Helena; Darlow, Christopher; Dold, Christina; Silva-Reyes, Laura; Blackwell, Luke; Lara-Tejero, Maria; Jiao, Xuyao; Stack, Gabrielle; Blohmke, Christoph J; Hill, Jennifer; Angus, Brian; Dougan, Gordon; Galán, Jorge; Pollard, Andrew J |
| Publisher Information: |
Springer Nature; //doi.org/10.1038/s41591-019-0505-4 |
| Publication Year: |
2020 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Acute Disease; Adolescent; Adult; Animals; Bacterial Toxins; Double-Blind Method; Humans; Mice; Inbred C57BL; Middle Aged; Salmonella typhi; Typhoid Fever; Young Adult |
| Description: |
Salmonella Typhi is a human host-restricted pathogen that is responsible for typhoid fever in approximately 10.9 million people annually1. The typhoid toxin is postulated to have a central role in disease pathogenesis, the establishment of chronic infection and human host restriction2-6. 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 model7. Forty healthy volunteers were randomized (1:1) to oral challenge with 104 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/xml; application/zip; application/pdf |
| Language: |
English |
| Relation: |
505; https://www.repository.cam.ac.uk/handle/1810/307498 |
| DOI: |
10.17863/CAM.54588 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/307498; https://doi.org/10.17863/CAM.54588 |
| Rights: |
Attribution 4.0 International (CC BY 4.0) ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.9EFE1A77 |
| Database: |
BASE |