Background and Aims:
Interruption of transmission of vaccine serotypes underlies effectiveness of pneumococcal conjugate vaccine programmes at population level. Nasal colonisation density varies widely between individuals and over time but its relationship to infectiousness is unknown. Streptococcus pneumoniae (Sp) nasal colonisation density is increased by upper respiratory viral infections and the live attenuated influenza vaccine (LAIV).  
In a multi-centre prospective randomised stepped-wedge trial, we are using LAIV as a probe to increase density of pneumococcal nasal carriage in LAIV-naive 2-year-olds and then assessing the impact on transmission rates to household contacts. 

Methods:
500 families with an eligible 2-year-old index child will be recruited over 2 seasons. Families are randomised 1:1 for the index child to receive LAIV at visit 1 or visit 3 (4 weeks later); saliva and nasopharyngeal samples (NPS) are collected from participants every two weeks over 2 months. Samples are analysed for Sp using real-time quantitative PCR (lytA). Samples are considered positive when the threshold cycle (Ct) value is less than or equal to 35.

Results:
Season 1 equating to 25% of total sample size
Families enrolled	123
Participants enrolled 421 
Participants per family (average) 3.43
NPS collected 1945
Saliva samples collected 2134

At Visit 1 (Bristol NPS data): 
Participant 	Carriage rate	Median density of carriage (Log10 gene copies/ml (range))
Index child	82%	3.28 (0.68-4.13)
Sibling	50%	2.74 (0.79-4.81)
Mother 	14%	1.06 (0.68-2.03)
Father	12%	1.19 (0.66-4.29)

Conclusion
These data confirm the feasibility of this study including high participation and completion rates per protocol. Pneumococcal carriage rates in all age groups are slightly higher than in our previous studies. This study exemplifies novel use of live attenuated vaccines as experimental probes in human challenge experiments to elucidate the biology of colonisation and transmission.

02 / A RANDOMISED PROSPECTIVE STEP-WEDGE MULTICENTRE STUDY TO EVALUATE THE RELATIONSHIP BETWEEN PNEUMOCOCCAL COLONISATION DENSITY IN 2-YEAR-OLD CHILDREN AND RATES OF TRANSMISSION TO FAMILY CONTACTS.