Understanding how Salmonella Typhi infects humans (Bottlenecks)

You are invited to take part in a study to investigate typhoid fever and how the typhoid bacteria causes disease.  The study is being run by the Oxford Vaccine Group which is part of the University of Oxford.

If you are aged 18 to 60 years old, in good health and live in the Oxford area, then you may be eligible to take part in the study. We will provide reimbursement for your time, inconvenience and travel. The total study participation time is 6 months.

Background

Typhoid fever is an infection caused by the bacteria Salmonella Typhi. Although typhoid fever is rare in the UK, it is a major problem in developing countries, affecting up to 22 million people and resulting in many deaths every year. Access to clean water and sanitation facilities could help to eradicate typhoid infection, however, this is difficult to implement in resource poor countries. The use of effective vaccines against typhoid could also help to control the spread of disease. The currently used typhoid vaccines are only moderately effective in preventing infection in people who have been immunised. New typhoid vaccines have been developed to overcome these problems, but more research and information is needed to study how well these vaccines work before they can be routinely used.

In this study, we are aiming to understand more about the Salmonella Typhi bacteria and how it causes disease. In particular, we want to understand how Salmonella Typhi can escape from the intestine, enter the bloodstream and cause typhoid fever. Our goals are to better understand typhoid fever and contribute to development of new vaccines against Salmonella Typhi.

Study Goals

In this study we will be undertaking a ‘challenge’ with two strains of the typhoid bacteria (Salmonella Typhi). Participants will be exposed to live Salmonella Typhi under tightly controlled circumstances, by asking them to swallow a drink that contains the bacteria. After the challenge we will closely monitor participants for a period of two weeks and treat participants with antibiotics as soon as they show any symptoms of infection.

Challenge with a single strain of Salmonella Typhi or Paratyphi has been undertaken by over 400 participants in previous Oxford Vaccine Group studies since 2011.

This study is designed to investigate the ‘bottlenecks’ hypothesis which suggests that just a single typhoid bacterium escaping into the bloodstream is enough to cause illness. Participants in this study will be challenged with a 1:1 ratio of a ‘normal’ strain of the typhoid bacteria, called the wild-type strain, and a modified strain of the typhoid bacteria that is not able to produce the typhoid toxin, called the toxin-negative strain. We know that by giving a specific dose of the wild-type strain of Salmonella Typhi, 60% to 70% of people exposed to the bacteria will develop typhoid infection. Participants taking a mixture of the bacteria will likely develop typhoid infection at the same rate. We will then look to see if the typhoid infection is caused by one or other of the two strains or both together. Whichever of these outcomes we detect will give us important information on how the Salmonella bacteria cause typhoid fever and could lead to new approaches to developing a vaccine against typhoid.

The Oxford Vaccine Group, University of Oxford, is based in the Centre for Clinical Vaccinology and Tropical Medicine in the Churchill Hospital site.

Further Information

Before you decide whether you would like to take part, it is important for you to understand exactly what the study is about and what participation would involve.

If you would like to find out more, please read the Study Information Booklet Study Information Booklet  and if you are interested in joining the study please visit https://trials.ovg.ox.ac.uk/trials/bottlenecks#webform-client-form-109  where you can access the screening questions and register your interest.

If you would like any further information regarding the study please contact us on:

Email info@ovg.ox.ac.uk, Tel: 01865 611400

Online Screening Questions

4. Have you lived in a country where there is typhoid disease for more than 6 months? (Typhoid is prevalent in the following regions: South Asia – e.g. India, Pakistan, Southeast Asia

 
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