Experimental human pneumococcal carriage

Plain English summary of protocol

Background and study aims
Pneumonia is a serious disease which causes swelling (inflammation) in the lungs and is usually caused by a pneumococcus bacterial infection. It is a major cause of death in children under five around the world. There are more than 90 different strains of pneumococcus and currently vaccines only cover around 13. In addition, strain replacement is also occurring, which means that the strains that used to cause disease that we now vaccinate against are being replaced by other strains for which we have no vaccine. There is therefore an urgent need for new vaccines. In most people pneumococcus can occasionally be found harmlessly inhabiting the nose where it does not cause any problem (pneumococcal carriage). About 10% of adults carry pneumococcus at any one time, and almost all adults experience an episode of carriage at least once per year. Carriage acts as a natural vaccine, boosting immunity against pneumococcal infection in adults and children. In order to develop an effective vaccine against pneumonia, it is important to understand how pneumococcal carriage acts to boost immunity. The aim of this study is to inoculate (place in the nose) people with varied doses of pneumococcal bacteria to determine the optimum dose for carriage (dose-ranging study) and then reproduce these findings in sufficient participants to be sure that we have a reproducible method (reproducibility study).

Who can participate?
Healthy adults who speak English fluently.

What does the study involve?
120 healthy participants (who have no current pneumococcal carriage) receive a small dose of live pneumococcal bacteria into each nostril, at a range of different concentrations. Six groups of participants are inoculated with a strain called serotype 23F and 60 with a strain called serotype 6B. After 48 hours and one week and 4 weeks, participants have samples taken from their nose to monitor the presence or absence of pneumococci. At 48 hours and four weeks, participants also have samples of blood and urine taken, as well as having a throat swab and samples taken from the lungs during a bronchoscopy and lavage (where a camera inserted into the lungs via the nose and the a small segment of the right lung is washed before cells are collected) procedure. If a participant becomes a carrier, they are given a three day course of antibiotics at the end of the study to ensure that the pneumococcus has been cleared.
60 additional participants are later recruited and randomly allocated to receive an inoculation of either serotype 23F or 6B, the concentration to use is determined from the first part of the study. After 48 hours and one week and 4 weeks, participants have samples taken from their nose to monitor the presence or absence of pneumococci. At 48 hours and four weeks, participants also have samples of blood and urine taken, as well as having a throat swab and samples taken from the lungs during a bronchoscopy and lavage.

What are the possible benefits and risks of participating?
There are no significant benefits to being involved in the study. Risks are related to blood tests, bronchoscopy (camera into the lungs via the nose) and inoculation (live bacteria put into the nose). Blood tests may cause minor pain or bruising. Inoculation carries a risk of infection including meningitis, pneumonia (chest infection, otitis media (ear infection) or sinusitis. Bronchoscopy carries a risk of chest pain, fever, infection, allergic reaction to sedation or anaesthetic throat spray, coughing up a small amount of blood, sore nose, sore throat, nose bleed, aspiration pneumonia (vomit going into your lungs if not starved of food and fluid before the bronchoscopy), cardiac arrhythmia (unusual heart rhythm and rate), and hoarse voice.

Where is the study run from?
1. Royal Liverpool Hospital (UK)
2. Liverpool School of Tropical Medicine (UK)

When is the study starting and how long is it expected to run for?
April 2011 to January 2013

Who is funding the study?
Bill and Melinda Gates Foundation (USA)

Who is the main contact?
Dr Andrea Collins

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

Royal Liverpool Hospital
Hospital/treatment centre

Research and Development
4th Floor Linda McCartney
Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
England
United Kingdom

"ROR"	https://ror.org/01ycr6b80

Funders

Funder type

Charity

Results and Publications

Study outputs

Editorial Notes

12/09/2023: Publication references added.
25/09/2017: Internal review.