Lung Innate Immunity and Microbiome after Tuberculosis Exposure (LIMBO-TB)

What is the purpose of this study?

We are a tuberculosis (TB) immunology and vaccine research group. We are trying to understand more about why some people get infected when they come into contact with someone with a TB infection while others do not.

TB is a disease caused by a bacteria (Mycobacterium tuberculosis). TB disease remains one of the top 10 causes of death worldwide. BCG, given as a single dose under the skin, is the only vaccine currently licenced for use against TB, but it is not always protective. The BCG vaccine works well against disease in childhood, but it is not good enough at protecting against disease in adulthood, which is when majority of TB deaths occur. We are working on developing better vaccines against TB and hope to use what we understand in this study to better protect people.

Why study people who are close contacts of TB patients?

TB is an infectious disease and worldwide it is estimated that 1 in 4 people are infected. However most people infected with the bacteria causing TB don’t get sick, and their bodies are able to fight off the infection or at least keep it at bay. Why some people are able to fight off or control the bacteria is not understood. Other people who come into contact with the TB bacteria don’t get infected at all, despite spending a lot of time with someone who is infectious. We suspect that there is something different about the body’s immune system which helps to protect some people.  If we can understand what this is, we may be able to develop better ways to protect and treat people.  Close contacts of those with TB infections are important to study as we know they have had lots of exposure to the bacteria, and allow us to investigate the very early stages of immune response

We will compare how the immune system responds in people who appear to have cleared the infection and those who have not, to understand more about the immune response and the bacteria that live in their airways (the microbiome)

Am I eligible to participate?

FAQ

What does it mean to have had close contact with someone with TB?

A “close contact” is someone who has spent significant time either living in the same house, or have spent a prolong period of time in the same physical environment (e.g. workplace or social settings) as someone with infectious TB. If you have been traced by the NHS TB contact tracing team you are likely to meet this definition for our study.

What is the microbiome?

The “Microbiome” is the name given to all of the bacteria that live on and in our bodies. Our skin, guts (intestines), mouth and throat are covered with bacteria all the time. These bacteria don’t make us sick and in fact we know that they are good at stopping us from becoming unwell. Changes in people’s microbiome has been associated with developing a range of medical problems, although we are only just beginning to understand why and how this happens. 

We know that the microbiome is important in ‘training’ our immune system, much less is known about how it effects the immune system during TB infections

What sort of samples will be collected in this study?

We are interested in measuring the immune responses to TB in people enrolled in this study. We will collect both blood samples, and also samples of phlegm (sputum). This allows us to explore what is happening in the lungs as well as the blood more generally.

We will also use the sputum samples to explore your respiratory microbiome. We know that microbiome is different in people who are unwell with TB compared to people who are not infected.

What if I don’t have a cough, how will you get the sputum (phlegm) samples?

We are not expecting people to have a cough so you will undergo a procedure called an induced sputum to help to loosen phlegm in your chest. This is a simple and safe procedure. You will be asked to breathe in a fine mist (aerosol) of salty water, this causes you to cough and helps bring up phlegm.

For full details of all visits, please read the participant information sheet group A & B / participant information sheet group C. 

Is there any reimbursement for the study?
Participants are reimbursed up to £100 for their time, travel and inconvenience. Full details of the reimbursement can be found in the the participant information sheet group A & B / participant information sheet group C. 

What are the advantages of taking part?

You will not necessarily gain any direct benefit from the study.  During pre-study assessment you will get information about your general health and lung function measurement. However, these assessments are not carried out for diagnostic purposes and should not be considered a substitute for a doctor’s visit.

Are there any risks from taking part in the study?

The main risks and side effects of the proposed study procedures are listed here. 

• Blood samples: drawing blood may cause slight pain and occasionally bruising
   
• Induced sputum procedure: This is a simple and safe procedure, for some people this may lead to coughing spasms. If this happened, you would be asked to stay in clinic until any coughing stops. Very rarely the salty saline may cause your airways to spasm. This is unlikely in people with no history of severe asthma and is quickly reversible with medication.  A sensation of shortness of breath may rarely be experienced during induced sputum procedures.

Please refer to the participant information sheet group A & B / participant information sheet group C for full details of procedures and potential risks. 

What will happen if I don't want to carry on with the study? 

Participation is voluntary and you are free to withdraw at any time. If you withdraw we would not perform any more research procedures, although occasionally we might offer you a follow up visit, for example, to check a blood result. With your permission, we would like to store the samples that we had already collected, but if you did not want this we would discard them. If you choose to withdraw from the study, your standard medical care will not be affected.

For more details about the study, see the: participant information sheet group A & B / participant information sheet group C. 

If you are interested in taking part, please click here to apply via the pre-screening questionnaire

If you have any other questions about participating then don’t hesitate to contact the study team by email at vaccinetrials@ndm.ox.ac.uk