This study is being conducted by a research team in the Department of Infectious Disease at Imperial College London and is funded by the Wellcome Trust.

Salmonella is a family of bacteria. There are over 2000 different types of Salmonella, each of which are subtly different. We are studying a type called “Salmonella Typhimurium”, which belongs to a group of Salmonella bacteria that we call non-typhoidal Salmonella – or NTS for short.

Salmonella (NTS) is a very big problem globally, but especially in sub-Saharan Africa. We think it affects over half-a-million people every year. In most healthy adults, Salmonella causes a gut infection (called gastroenteritis). This normally leads to diarrhoea, stomach-ache, and fever.

However, in other parts of the world (mainly sub-Saharan Africa), Salmonella (NTS) infection can be much more severe. It can get inside the bloodstream or parts of the body outside the gut. This more severe form almost exclusively occurs in vulnerable groups of people who have a poorly functioning immune system (e.g. advanced HIV infection), or those who are young (children under 5 years old), very old, or with specific risk factors like malaria or sickle cell disease.

There aren’t any vaccines against the group of Salmonella (NTS) that we’re studying. Some groups are testing candidate Salmonella (NTS) vaccines in early-stage trials. These vaccines look promising, but more research is needed. Our group is studying Salmonella (NTS) because in the future we want to help test new vaccines to prevent this illness.

We are going to research Salmonella (NTS) by developing a special type of clinical study called a human challenge study.

A human challenge (or infection) study is a carefully managed medical research study, during which volunteers are intentionally given an infection in a safe way with healthcare support. These studies are done to understand diseases and find new ways to prevent and treat them. You can read more about human challenge studies in general on the HIC-Vac website.

This is the first time that a non-typhoidal Salmonella human challenge has been carried out, but we have lot of experience of performing challenge studies for similar bacterial infections (like typhoid fever) and for other diseases (influenza, COVID-19).

Past human challenge studies have been extremely useful in the development of vaccines for similar gut infections (typhoid fever and cholera). In the future we plan to use the model to test new vaccines to protect people against Salmonella (NTS).

We will be giving volunteers one of two strains of Salmonella (Salmonella Typhimurium) in a drink that contains the bacteria. After the challenge we will closely monitor volunteers for a period of around two weeks. The first week will involve staying in quarantine in a hospital (either Hammersmith or Chelsea and Westminster Hospital). We expect most participants will stay in quarantine for 7 days, but there is a chance we will ask you to stay longer if you still have symptoms. Following discharge from the quarantine unit, you will need to come to the clinic daily for the next 7 days, then a further 4 to 9 follow-up visits spread over a year.

We will use two strains of the Salmonella Typhimurium bacteria. Half of the volunteers in this study will be challenged with a strain of Salmonella that is common in the UK and other half will be challenged with a strain that originated in Malawi. There is some data from the lab which suggests that these bacteria behave differently, but we don’t yet know the significance of this in healthy people.

This study is called a “dose escalation” study. This means that we start the challenge with a low dose of bacteria (to make sure it’s safe) and gradually increase (or decrease) until about 60% to 75% of people exposed to the bacteria develop certain symptoms of a Salmonella (NTS) infection. We will be able to study how the immune system responds to the different strains of Salmonella (NTS), to understand it prevents Salmonella (NTS) disease. This will add to our general understanding of the bacteria.

We will treat study volunteers with antibiotics when they show specific symptoms of infection, such as moderate to severe diarrhoea or fever. If no symptoms develop, we will offer everyone who has tested positive for a Salmonella (NTS) infection antibiotics at day 14 to ensure the infection is completely cleared up.

We are recruiting up to 80 healthy volunteers who are:

-          aged between 18 to 50 years of age

-          healthy with no underlying medical conditions

You will have your own room and ensuite facilities. There will be TV and Wifi, and you can bring your own personal devices (laptop, mobile phone, games console) so you can work, study, keep in touch with friends and family, and entertain yourself during quarantine. You may also bring small items for exercise (for example a yoga mat).

Taking part will not improve anyone’s health, although you might benefit from a general health check at screening. Study volunteers will be compensated for their time, travel and inconvenience if they take part (up to £3,237).

We have designed the study in such a way as to minimise the risk. The risk of taking part in this study is low but – as we are deliberately infecting healthy volunteers – this risk is not zero. It is very important that you read the Study Information Booklet in full for details of what the potential risks are, so that you can make an informed decision.

Summary of the risks: (here is a link to an accessible version)

The most likely risk is to develop gastroenteritis. This usually presents with any of the following symptoms:

• Diarrhoea
• Stomach-ache
• Fever
• Vomiting
• Loss of appetite

Some people may develop a headache, may feel tired and generally unwell, with muscle or joint aches. Some people may notice blood in their stool (poo). The time from exposure to developing symptoms is about 12-48 hours, but can range from 4 hours to 3 days before symptoms start. Overall symptoms usually last 4 to 7 days.

In healthy young people, Salmonella gastroenteritis will usually get better by itself without any specific treatment. During the time we expect you to develop symptoms, you will be closely monitored in the quarantine unit.

We will protect against dehydration caused by diarrhoea by providing you with plenty of fluids and guide you on how much (and how frequently) you will need should drink. We can also give you fluids into a vein via a drip if needed.

We know that antibiotics will normally help the symptoms get better faster, so we will treat all volunteers with antibiotics when they develop certain symptoms. Once Salmonella (NTS) infection has been confirmed, doctors can offer you other treatments to help with symptoms like fever, headaches and vomiting.  

The screening, quarantine stay and follow-up clinics will take place at one of three locations:

·         Hammersmith Hospital, Du Cane Road, London W12 0HS (find location here on Google maps Hammersmith Hospital)

·         Charing Cross Hospital, Fulham Palace Road, W6 8RF (find location here on Google maps Charing Cross Hospital)

·         Chelsea & Westminster Hospital, 369 Fulham Road, London, SW10 9NH (find location here on Google maps Chelsea & Westminster Hospital)

For information on how to travel to the sites, please click on the links above.

Review by an ethics committee is one of a series of safeguards intended to protect people taking part in all clinical research studies. It is a thorough process and there are many principles that are considered during the review, including weighing up the benefits against the risks. Another important consideration is making sure the potential participants receive high-quality, comprehensive information about the study in a timely fashion. The information about the human infection study sent to and discussed with potential volunteers is very detailed and there are measures in place to make sure it is understood, so potential volunteers have a full picture of what the risks are and what the study entails before agreeing to take part (this is known as informed consent).

This study was reviewed by London – Fulham Research Ethics Committee and approved on 28th April, 2023.

You can find out more about Research Ethics Committees (RECs) and the Health Research Authority (HRA) approvals on the HRA website. A REC is made up of experts from different backgrounds (for example doctors, clinical trial experts, and scientists) and members of the public.

News stories

CHANTS at the Great Exhibition Road Festival, 2023

How can a human challenge study help tackle the global impact of Salmonella? 

Publications

Smith C, Smith E, Chiu C et al. The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK [version 1; peer review: 1 approved]. Wellcome Open Res 2023, 8:111 (article in Wellcome Open Research)

All human challenge news stories

Find more news about other human challenge studies at Imperial.