Pneumococcal pneumonia

Transcription

1 Pneumococcal pneumonia Wei Shen Lim Consultant Respiratory Physician & Honorary Professor of Medicine Nottingham University Hospitals NHS Trust University of Nottingham

2 Declarations of interest Unrestricted investigator-initiated research funding from Pfizer to Nottingham University Hospitals NHS Trust: pneumonia study. WSL Chief Investigator. Was Member of NICE Pneumonia GDG. Developed the CURB65 pneumonia mortality risk score Views expressed are my own.

3 Clinical case 69 year old man Unwell a few days only. Fever, cough, green sputum. Very tried. Loss of appetite. Hypertension. Fit and well. Retired fibre glass factory Temp 38 C Pulse 110/min BP 110/60 Resp rate 20/min Hb 120 WCC 12 Platelets 628 CRP 95 Urea 4.0 Creat 63

4 Infection? Pathogen? A B C D E F

5 Is this an infection? What is the pathogen?

6 British Thoracic Society National CAP audit (n=24,180) Mean age 72 years (range: ) Female 53% Admitted from care facility 15.7% 65 years old

7 British Thoracic Society National CAP audit (n=24,180) n (%) COPD 5398 (22.3) Chronic Heart Disease 5269 (21.8) Chronic lung disease 2940 (12.2) Stroke 2450 (10.1) Congestive Cardiac Failure 2002 (8.2) Malignancy 1772 (7.3) Chronic Kidney Disease 1868 (7.7) Liver disease 251 (1.0)

8 Microbiology of CAP (UK): pre-pcvs Pathogen identified 75% Single pathogen 46% Bacteria 54% Virus 23% Atypical pathogen 22% Lim, Thorax 2001

9 UK IPD: 2000 to 2013 Waight Lancet ID 2015

10 NP carriage (<5 yr olds): Southampton NVT Carriage rate PCV13 PCV7 Devine, Vaccine 2017

11 Post-PCV effects on SPn carriage (Sweden) Vaccination programme 2007: PCV7 à 2010: PCV13 NP samples 2004 (n=260) and (n=2161) PCV13 serotypes Galanis ERJ 2016

12 Pneumococcal CAP in adults (UK) SPn Non-PCV / /13 Rodrigo, ERJ 2015

13 US CDC study. 5 hospitals ( ) 2488 of 3634 eligible adults (68%) with CAP US Jain low burden of SPn * * * * * Jain NEJM 2015

14 Pneumococcal serotypes: Canada CAP: 3851 adults - any test done 14% SPn 621 adults 4 tests done 23% SPn n=231 n= 72 n=132 LeBlanc, Vaccine 2017

15 CAP microbiology: Spain Menendez Vaccine 2017

16 Pneumococcal serotypes in Spain CAP 1258 adults 29% SPn (n=368) 400 No. of cases non-pcv13 PCV % % 1 2 CAP SPn (n=368) IPD SPn (n=65) Menendez Vaccine 2017

17 Serotypes in CAP : novel 24-serotype assay UK Sep 2014 to Sep Adults with CAP n=667. Of 481 participants (consent + samples) à 40% SPn % PPV23 N o o f c a s e s % PCV A 6 B 7 F 9 V C 1 9 A 1 9 A /F 2 3 F N 1 0 A 1 1 A 1 2 F 1 5 B 1 7 F F 3 3 F 1 6 F 3 8 U n t y p e d Eletu, CVI 2017 Daniel et al. Manuscript

18 Pneumococcal CAP in adults (UK) SPn Non-PCV13 PCV / / /15 Rodrigo, ERJ 2015

19 Pneumococcal CAP in adults (UK) SPn? Non-PCV13? PCV13 serotype / / /15 Rodrigo, ERJ 2015, Daniel, submitted

20 UK population projections mid-2041 mid-2016 People aged 85 and over: mid million mid million Source: ONS

21 Serotypes in CAP : novel 24-valent assay UK All CAP SPn CAP n=481 n=196 Severity (CURB65 score) Low 48% 46% Moderate 29% 27% High 22% 27% Outcomes LOS (days) 7 (4 11) 7 (4-10) ICU admission 8% 10% 30-d mortality 8% 8% Daniel et al. Manuscript

22 Treatment of pneumococcal infection Pneumococcal bacteraemia all age-groups (US) Before penicillin ( ) After penicillin ( ) ( ) Watson, CID 1993

23 Resistance: Streptococcus pneumoniae (US) IPD surveillance (US) Tomczyk, CID 2016

24 Resistance: Streptococcus pneumoniae (UK) Proportions with triple resistance: IPD (blood, CSF), PHE (n = 13,551) X * * ** * X * X = not in PCV13 Shepphard, Eurosurv 2016

25 NICE Pneumonia Guideline Dec 2014 Low severity CAP à single antibiotic Moderate-High severity CAP à dual antibiotics (macrolide + beta-lactam) Low Moderate High BTS National CAP Audit dataset Priya D, Thorax 2016

26 Antibiotic therapy: Systematic Review mortality < 5% combination better monotherapy better Lee, JAMA 2016

27 Pneumococcal seasonality: RSV, Flu US in-patient dataset >16,000 pneumococcal hospitalisations in children. RSV Influenza Weinberger, PlosMed 2015

28 RSV increases pneumococcal virulence Adherence Cilary dyskinesis Smith, AJRCCM 2014

29 Viral pathogens in CAP Overall: 24.5% viral pathogens Odds of IP/30-day mortality: Any viral infection OR 1.3 (9 5% CI ) Dual viral-bacterial infection OR 2.1 (95% CI ) Burk, ERR 2015

30 J Infection, March 2017,; Nature Biotech, 2015

31 as of January March, 2015 Antibodies Probiotics Lysins Bacteriophages Immune stimulation Peptides C difficile P aeruginosa S aureus Urinary tract infection Lancet ID 2016

32 Research investments for UK infectious disease research A systematic analysis of awards to UK institutions median Log-transformed UK research investment by UK mortality Head, J Infect (in press)

33 Global Burden of Disease 2015 study Lower Respiratory Tract Infections in 195 countries 5 th leading cause of death (of 249 causes) 1 st leading infectious cause of death All ages 37 per 100, million <5 year olds 105 per 100, million >70 year olds 1.27 million 2 nd leading cause of DALYs after IHD Mortality per 100,000 < 5 yrs old > 70 yrs old China USA Japan Lancet ID, 2017

34 LRI mortality in <5-year olds Western sub-saharan Africa Western Europe socio-demographic index Attributable fraction: LRI mortality Lancet ID, 2017

35 Summary: Pneumococcal pneumonia Despite vaccines, burden of disease remains HIGH Global inequalities Dynamic epidemiology - vaccine & antibiotic pressures Diagnosis remains a challenge Despite antibiotics, significant morbidity and mortality Viral interactions New treatments needed Appropriate research investment Avoid over-confidence, combat nihilism