Investigating Typhoid Fever Pathogenesis (TYGER)
Research type
Research Study
Full title
Investigating the role of typhoid toxin in the pathogenesis of enteric fever: A double-blinded, randomised, outpatient human challenge study.
IRAS ID
205635
Contact name
Andrew Pollard
Contact email
Sponsor organisation
Clinical Trials and Research Governance, University of Oxford
Duration of Study in the UK
1 years, 11 months, 31 days
Research summary
Typhoid fever results from infection with a bacterium called Salmonella Typhi and is a major cause of illness worldwide. It is estimated to infect 20-25 million people every year and can affect people of all ages, but is particularly common in young children. The disease is spread through contaminated food and water, and efforts to improve water quality, sanitation and hygiene will likely go a long way to reducing the global burden of disease. Unfortunately, improving access to clean water and sanitation improvements is very costly and difficult to implement on a large scale. Vaccination against typhoid fever is likely to be a cost effective way of reducing the global disease burden.
There are two vaccines currently available against typhoid fever. Whilst these vaccines provide some protection against disease (in the region of 50-70%) these vaccines are less effective in young children, who are the population group at highest risk of disease. In order to develop a new generation of typhoid vaccines it is important to have a more complete understanding of how the bacterium causes disease.
In this study, we are aiming to understand more about the Salmonella Typhi bacteria and how it causes disease. In particular, we aim to study the importance of a toxin produced by the typhoid bacteria, called the typhoid toxin. The typhoid toxin has only recently been discovered. It is made only by the typhoid bacteria and closely related bacteria, such as paratyphoid. From studies done in the laboratory, there is evidence that the typhoid toxin is important in causing typhoid disease. It is thought that the typhoid toxin might be important in causing symptoms of typhoid disease, however the exact role of the typhoid toxin during infection in humans hasn’t been studied before. Studying this might impact on how we design new vaccines against typhoid.
In this study we will be undertaking a ‘challenge’ with two strains of the typhoid bacteria (Salmonella Typhi). This involves exposing participants to live Salmonella Typhi under tightly controlled circumstances, by asking them to swallow a solution that contains the bacteria. After the challenge we closely monitor participants for a period of two weeks and we will then treat participants with antibiotics as soon as they are diagnosed with typhoid disease. We are interested in comparing the response to challenge between two strains of the typhoid bacteria that differ in the production of the typhoid toxin. This process has been undertaken by participants in previous Oxford Vaccine Group studies since 2011.
This study is funded by the Bill & Melinda Gates Foundation.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
16/SC/0358
Date of REC Opinion
14 Jul 2016
REC opinion
Favourable Opinion