Investigating Typhoid Fever Pathogenesis

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, the investigators are aiming to understand more about the Salmonella Typhi bacteria and how it causes disease. In particular, the investigators 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 the design new vaccines against typhoid.

In this study, the investigators will be undertaking a 'challenge' with two strains of the typhoid bacteria (Salmonella Typhi). This involves exposing participants to live Salmonella Typhi under defined circumstances, by asking them to swallow a solution that contains the bacteria. After the challenge the investigators closely monitor participants for a period of at least two weeks and the investigators will then treat participants with antibiotics as soon as they are diagnosed with typhoid disease. The investigators 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.

Conditions

• Salmonella Typhi Infection

Interventions

OTHER

Salmonella Typhi (S. Typhi)

Investigating the role of typhoid toxin in the pathogenesis of enteric fever

Sponsors & Collaborators

• Bill and Melinda Gates Foundation

  collaborator OTHER

• Yale University

  collaborator OTHER

• University of Oxford

  lead OTHER

Principal Investigators

• Andrew J Pollard · Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Oxford, Oxfordshire, United Kingdom, OX3 7LE

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-02-27

Primary Completion

2018-08-15

Completion

2022-09-30

Countries

• United Kingdom

Study Locations