Streptococcus pneumoniae infection Infections and Infestations Pneumonia due to Streptococcus pneumoniae
Conditions
Interventions
A single blind randomised controlled trial design allows an unbiased methods for comparison of four groups comparing S. pneumoniae i) attenuated strain I, ii) attenuated strain, II iii) wild type bact
Sponsors
Liverpool School of Tropical Medicine
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy volunteers 2. Age 18 – 50 years 3. Capacity to give informed consent 4. Ability to speak fluent English
Exclusion criteria
Exclusion criteria: 1. Research participant currently involved in another study unless observational or non-interventional 2. Participant in a previous EHPC trial 3. Natural carriers of S. pneumoniae identified following initial screening* 4. Vaccination: pneumococcal vaccination (routine in UK babies born since 2005 or US 2001) 5. Allergic to penicillin, amoxicillin 6. Health history: 6.1. Chronic ill health including, immunosuppressive history, diabetes, asthma (on regular medication), recurrent otitis media or other respiratory disease 6.2. Medication that may affect the immune system or clotting e.g. steroids, inflammation altering (e.g. nasal steroids, roacutane or aspirin) 6.3. Recent antibiotics (within the last 4 weeks or long term for known active chronic infection) 6.4. Splenectomy 6.5. Current acute severe febrile illness 6.6. Major pneumococcal illness requiring hospitalization 6.7. Other conditions considered by the clinical team as a concern for participant safety or integrity of the study 7. Direct caring role or close contact with individuals at higher risk of infection: 7.1. Children under 5 years age 7.2. Chronic ill health or immunosuppressed adults 7.3. Adults over the age of 75 years 8. Smoker: 8.1. Current or ex-smoker in the last 6 months 8.2. Significant smoking history - more than 20 cigarettes per day for 10 years or the equivalent (> 10 pack years) 9. Women of child-bearing potential (WOCBP) who are: 9.1. Not deemed to have sufficient/effective birth control or confirmed abstinence 9.2. Pregnant 10. History of drug or alcohol abuse (at discretion of the clinician) 11. Overseas travel planned in follow up period (if unplanned contact team)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The efficacy of nasal administration of attenuated Streptococcus pneumoniae strains to induce mucosal immunity thereby prevent future colonisation with wild type Streptococcus pneumoniae using the Experimental Human Pneumococcal Challenge Model; Timepoint(s): Participants are challenged with the wild type 6B at six months post inoculation. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Antibodies and cellular adaptive immune responses local and systemic to S. pneumoniae pre and post colonisation 2. The presence, density and duration of pneumococcus measured using classical microbiological and qPCR techniques on nasal wash collected following inoculation on day, 2, 6, 16, 22, 27 or 36 and after challenge on day 2, 6 or 14 3. Sequencing and in vitro testing of bacteria recovered to ensure genome and phenotypic stability 4. Presence of S. pneumoniae in nasal wash following cultures when carriage positive at each study visit 2, 6, 16, 22, 27 or 36 and after challenge on day 2, 6 or 14 5. Presence of S. pneumoniae on hand swabs or culture plate following standard microbiology cultures when carriage positive at selected visits subject to carriage status | — |
Countries
England, United Kingdom
Outcome results
None listed