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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

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Dr Adam Finn @ MRF's Meningitis & Septicaemia in children & Adults 2017

  1. 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. 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. 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. 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. 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. 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

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