Dr Adam Finn @ MRF's Meningitis & Septicaemia in children & Adults 2017
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Developments in the detection and understanding of meningococcal carriage, and implications for studies of the impact of MenB vaccines https://www.meningitis.org/mrf-conference-2017
Dr Adam Finn @ MRF's Meningitis & Septicaemia in children & Adults 2017
•1 like•7,357 views
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Developments in the detection and understanding of meningococcal carriage, and implications for studies of the impact of MenB vaccines https://www.meningitis.org/mrf-conference-2017
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Dr Adam Finn @ MRF's Meningitis & Septicaemia in children & Adults 2017
- 1. 15/11/2017 1 Developments in the detection and understanding of meningococcal carriage and implications for studies of the impact of MenB vaccines @adamhfinn MRF London 15th Nov 2017 tinyurl.com/adammrf2017 MenC changing schedules Birth 10 years 20 years ACYW tinyurl.com/adammrf2017 MenW cases in England, 2005/06-2014/15 tinyurl.com/adammrf2017 Cortesia de S Ladhani, PHE, RU Cortesia de S Ladhani, PHE, RU 2014/15 2015/16 2016/17 UK cumulative incidence of MenB cases by age group 2011-2017 tinyurl.com/adammrf2017 Secondary endpoints 4CMenB vaccine MenB Controls Efficacy 95% CI All B 233/2489 9.4% 262/2576 10.2% +15.6% -11.0 to +35.9% All Nm 797/2489 32.0% 885/2576 34.4% +18.2% +3.4 to +30.8% B C W Y 449/2489 18.0% 539/2576 20.9% +26.6% +10.5 to +39.9% Read et al., ESPID 2013, Lancettinyurl.com/adammrf2017 Carriage studies • Pfizer study – freezing and batching • Portugal 1 – PCR and cx-amp PCR • BrisMenNHC - longitudinal – (MRF1) virology; GSK genogrouping • Portugal 2 – saliva • SPIT (MRF2&3) – lots more saliva • Better understanding of biology • Better sampling and lab methods tinyurl.com/adammrf2017
- 2. 15/11/2017 2 Throat Swabs / OPS Direct plating Stored STGG broth qPCR tinyurl.com/adammrf2017 Meningococcal carriage density in 87 young adults 0 5 10 15 20 25 30 35 40 45 50 0 to <10 10 to <100 100 to <1000 1000 to <10000 CFU/ml Number of students tinyurl.com/adammrf2017 Mening’ carriage density Finn et al PIDJ 2016 Culture – left/hatched qPCR – right/solid Upper grey sections non-concordant results tinyurl.com/adammrf2017 tinyurl.com/adammrf20 17 Oxford Bristol V1 V2 V3 V4 V5 V6 Other centres V V 15-19 year olds Into 1.5ml STGG broth on site Meningococci determined by q-PCR for sodC Xfer to lab within 2-6 hours frozen -80 °C Swab and questionnaire at each time point £5 thank you for their time for V2-6 BrisMenNHC Density over time within individuals appears highly variable tinyurl.com/adammrf20 17 0 1000 2000 3000 4000 5000 6000 Gene copies/ml Visit date Density over time within individuals appears highly variable tinyurl.com/adammrf20 17 0 1000 2000 3000 4000 5000 Gene copies/ml Visit date
- 3. 15/11/2017 3 Density over time within individuals appears highly variable tinyurl.com/adammrf20 17 0 200 400 600 800 1000 1200 Gene copies/ml Visit date Density over time within individuals appears highly variable tinyurl.com/adammrf20 17 0 500 1000 1500 2000 2500 Gene copies/ml Visit date Density over time within individuals appears highly variable tinyurl.com/adammrf20 17 0 2000 4000 6000 8000 10000 12000 14000 16000 18000 Gene copies/ml Visit date tinyurl.com/adammrf20 17 Characteristic Group coeff 95% CI p Gender Female* 0 (reference) 0.020 Male 0.40 0.06 0.73 Age group 15/16 0.15 -0.24 0.54 0.218 17* 0 (reference) 18 -0.38 -0.80 0.03 19 0.38 -1.12 1.88 School year Year 12* 0 (reference) 0.006 Year 13 0.70 0.27 1.14 Other 0.18 -1.77 2.14 Ethnicity White* 0 (reference) 0.033 Asian -0.61 -1.27 0.04 Black 0.50 -0.31 1.32 Mixed/other -0.76 -1.53 0.01 Antibiotic use None* 0 (reference) 0.073 Stopped in last month0.67 -0.04 1.39 Stopped in last week 0.15 -0.79 1.08 Currently using -0.68 -1.41 0.05 Pub days in week 0* 0 (reference) 0.068 1 0.10 -0.19 0.38 2–7 0.54 0.08 0.99 Has smoker GF/BF No* 0 (reference) 0.076 Yes -0.94 -1.98 0.10 Month of year Jan* 0.00 0.00 0.00 0.193 Feb 0.02 -0.37 0.40 Mar -0.12 -0.51 0.27 Apr 0.00 -0.44 0.44 May -0.37 -0.88 0.14 Sep -0.70 -1.34 -0.06 Oct -0.16 -0.64 0.32 Nov 0.15 -0.27 0.58 Dec 0.17 -0.34 0.68 Constant -1.33 -1.79 -0.86 0.000 We found • Gender • School year • Ethnicity • Antibiotic use • Pub visits • Partner who smokes were associated with Nm density Density vs. month tinyurl.com/adammrf2017 Associations between Meningococcal Carriage &: P=0.0564 P=0.0354 N. meningitidis+ N. meningitidis- Total Virus+ 14 105 119 Virus- 88 1173 1261 Total 102 1278 1380 RhV+ 12 81 93 RhV- 90 1197 1287 Total 102 1278 1380 Rhinovirus Presence Virus Presence N.B. Percentages as a proportion of total Viral/RhV +/- 12.9% 87.1% 100% 7.0% 93.0% 100% 11.8% 88.2% 100% 7.0% 93.0% 100% tinyurl.com/adammrf2017
- 4. 15/11/2017 4 Results-By Calendar Month 0 2 4 6 8 1 0 1 2 1 5 2 0 2 5 M o n th Percentage(%) F lu A R S V R h V N . m e n in g it id is S e p O ct N o v D e c J a n F e b M a r A p r 2 30 2 30 2 200 1 38 2 56 2 46 60n = tinyurl.com/adammrf2017 See Liz Oliver’s poster here Comparing methods tinyurl.com/adammrf2017 1 45 87 2442 121 1493 46 66 1614 Culture PCR Culture amplified PCR Cx 7.6% PCR 8.8% Cx+PCR 11.4% CaPCR 15.9% Cx+PCR+CaPCR 18.3% Multiple genogroups Ø 5 of the 1,813 samples detect multiple genogroups in one sample run of qPCR and the relevant Ct values Ø Ct £ 36 – positive for Nm generic sodC and genogroups B, C, W, X and Y. tinyurl.com/adammrf2017 See Kirsty Nelson’s poster here Saliva tinyurl.com/adammrf2017 Increasing sensitivity… tinyurl.com/adammrf2017 N=1005 18-25 year old medical/pharmacy students Coimbra, Portugal Increasing sensitivity… tinyurl.com/adammrf2017
- 5. 15/11/2017 5 All meningococci - PCR tinyurl.com/adammrf2017 Throat swabsSaliva Direct Culture-amp’d 126 72 54 71 12.5% 19.6% 33.1% 136 34 33 5 20 23 11 52 14 5 36.1% 119 17 30 25 8 11 12 1419 6 GpB meningococci - PCR tinyurl.com/adammrf2017 Throat swabsSaliva Direct Culture-amp’d PCR 1.7% +caPCR 3.1% +Sal 3.3% 2 0 8 3 12 14 1+caPCR 3.6% 1 1 3 0 0 1 3 0 1 Gps BWXY meningococci - PCR tinyurl.com/adammrf2017 Throat swabsSaliva Direct Culture-amp’d PCR 2.2% +caPCR 4.4% +Sal 5.0% 4 0 10 3 19 14 1+caPCR 5.5% 4 2 5 0 1 1 3 0 2 SPIT • 433 16-18 year olds – 419/397/296 V1-3 – Approx. 50% participation • All offered 2 doses Bexsero • OPS at vaccine visits & 3 months later – 71% of V1s came for final swab • Weekly salivas from pre-vaccine to end • MRF have funded direct sodC PCR from all OPS and salivas. Further funding needed • Questionnaires on demographics and motivation to take part…see Nicola Kelly’s poster heretinyurl.com/adammrf2017 SPIT study OPS/Saliva samples tinyurl.com/adammrf2017 NanoString nCounter system Gene detection & counting nCounter tinyurl.com/adammrf2017
- 6. 15/11/2017 6 Conclusions • Meningococcal carriage density is dynamic – possibly driven by viral infections • Overall crude carriage rates in vaccine recipients may be relatively poor predictors of vaccine impact on transmission • Viable meningococci can be found in saliva – implications for transmission and precautions tinyurl.com/adammrf2017 Conclusions • Significant sampling and laboratory methodological advances now available to make carriage studies more sensitive and informative. • IMD not that rare – spend money on vaccines not lottery tickets! • Thanks to MRF for support tinyurl.com/adammrf2017