Sir William Osler Streptococcus pneumonia ( pneumococcus ) “the captain of all the men of death”

1. Sir William Osler Streptococcus pneumonia (pneumococcus) “the captain of all the men of death” “Pneumonia may well be called the friend of the aged. Taken off by it in an acute, short, not often painful illness, the old man escapes those ‘cold gradations of decay’ so distressing of himself and to his friends”

2. Pneumonia • 1-2 million deaths per year • Half in children • Commonest infectious cause of death in • developed countries • About 1 in 500 people age >55yr per annum Sir William Osler Streptococcus pneumonia (poneumococcus) “the captain of all the men of death” “Pneumonia may well be called the friend of the aged. Taken off by it in an acute, short, not often painful illness, the old man escapes those ‘cold gradations of decay’ so distressing of himself and to his friends”

3. Pneumonia Severity : CURB 65 • 1068 patients admitted to 3 hospitals • 9% mortality at 30 days Lim Thorax 2008

4. Pneumococcal disease and age

5. Risks of Pneumococcal disease OR (95%CI) Males 2.7 (1.7-3.4) Smoker 4.1 (2.4-7.3) Less than high school 2.8 (1.3-5.9) <6yr child in day care 3.0 (1.5-6.2) Chronic disease 2.6 (1.4 -5.1) COPD, diabetes, cirrhosis, heart failure) Case control study Atlanta, Baltimore, Ontario 228 cases of Invasive pneumococcal disease Excluded immunosuppressed inc cancer Nuorti New Eng J Med 2001

6. 10% of healthy adults. • 20–40% of healthy children • 60% of infants and children in nurseries

7. Toffee apple • 92 different serotypes • 70 % of adult infection and 80% of childhood infection caused by 10 types

8. Polysaccharide vaccine (23 valent) Pneumovax II Conjugated polysaccharide vaccine Prevanar (13 valent) £8.32 £49.10 (x 3)

9. Components of pneumococcal vaccines • 23 valent Polysaccharide vaccine • 78% of serotypes age group 18-49 • 76% of serotypes age group 50-64 • 66% of serotypes age group >64 • 13 valent conjugate vaccine • 53% of serotypes age group 18-49 • 49% of serotypes age group 50-64 • 44% of serotypes age group >64

10. Pneumococcal vaccine timelines • 1977 14 valent polysaccharide vaccine • 1983 current 23 valentpolysaccharide vaccine • 1992 vaccine recommended for at risk groups • 2002 conjugate vaccine 7 for at-risk children <2yr • 2003 polysaccharide vaccine for everyone ≥ 65 yr • 2004 conjugate vaccine for at-risk children <5 yr • 2006 routine childhood immunisation • 2010 13 valent conjugate vaccine introduced

11. Effectiveness of pneumococcal vaccine Isolation of PCV-7 pneumococcal strains in those age <2yr Public Health England

12. Adverse effects • Fever nausea, headache 1:1000 • Deaths 0 • Local reaction (unable to lift arm) • First vaccine 1% • Reimmunisation 5% • Elderly female, lax skin 10% Mantani Lancet 2003

13. Invasive pneumococcal disease vs pneumonia

14. Time to discharge Time to achieve clinical stability Probability of dying Pneumococcal bacteraemia and outcome of pneumonia • 125 subjects with bacteremic • 1,847 subjects without Bordon Chest 2008

15. 25 studies 18 RCTs with 64,852 subjects; 7 non-RCTs with 62,294 subjects) • Effective against invasive pneumococcal disease (IPD) • 74% reduction (OR 0.26, 95% CI 0.14 to 0.45) • Effective against pneumonia in low-income countries • 46% reduction (OR 0.54, 95% CI 0.43 to 0.67) • No significant effect against pneumonia in high-income countries (OR 0.71, 95% CI 0.45 to 1.12) • Less effective in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19) • No reduction in mortality (OR 0.90, 95% CI 0.74 to 1.09)

17. Duration of protection from pneumococcal polysaccharide vaccine Pneumococcal antibody levels Vaccine effectiveness (%) by age and time from vaccination <3 3-5 >5 <3 3-5 >5 <3 3-5 >5 <55 55-64 65-74 Shapiro New Eng J Med 1991

18. Effectiveness of pneumococcal vaccine Isolation of PCV-7 pneumococcal strains in those age <2yr Public Health England

19. Herd effectiveness of pneumococcal vaccine Isolation of PCV-7 pneumococcal strains in those age >5yr Public Health England

20. Emergence of non PCV-7 pneumococcal strains Isolation of non- PCV-7 pneumococcal strains in those age >5yr Public Health England

21. Pneumococcal promiscuity

22. Pneumococal vaccine in adults • Effectiveness against pneumonia is uncertain • Stops bacteraemia • May just stop bacteraemia • Duration of effectiveness is uncertain • Changing epidemiology of pneumococcal disease

26. Death from pneumonia in metal working occupations 1930-1963

27. Death from pneumonia in metal working occupations 1979-1990

28. Death from pneumonia in metal working occupations 1991-2000 Pneumococcal and unspecified lobar pneumonia (ICD 481) Bronchopneumonia (ICD 481) Other pneumonias (ICD 480, 482-3, 486)

30. Effects of metal fume exposure • Consistent x 2-3 increased risk of pneumonia • Hasn’t decreased since the 1930s • Only when actively exposed • Confined to lobar/ pneumococcal pneumonia WHY ?

32. Iron and welding • Iron facilitates bacterial growth • Iron increases inflammation • Iron is toxic to macrophages

33. The Iron war during infection • Pathogens adapt to obtain Iron • Produce haemolysins which liberate iron from haem • Produce proteolytic proteins that break down transferrin and lactoferrin • producing their own low molecular weight iron chelators, • Host organisms restrict iron availability during infection. • Lactoferrin, ferratin bind iron • Decreased binding to transferrin • Macrophages ingest Fe-transferrin • Reduced release of Fe from macrophages • Decreased absorption of Iron ;" " while the amount of iron bound

34. Welding and pneumonia • 75,000 welders in the UK • 40-50 hospital admissions pa because of fume • 2 deaths pa Source : HSE

35. PPV (single 0.5ml dose in those who have not received PPV previously) should be considered for those at risk of frequent or continuous occupational exposure to metal fume (e.g. welders) taking into account the exposure control measures in place. Vaccination may reduce the risk of invasive pneumococcal disease but should not replace the need for measures to prevent or reduce exposure.

36. Pneumococcal disease 1 in 5000 welders/yr • Vaccine reduces risk by 75% • Effect lasts 10 yr • Vaccinating 600 welders will prevent 1 case pa • If 1 in 8 die • Vaccinating 5000 welders will prevent 1 death pa

38. Number needed to treat Stopping smoking to prevent IHD death 8 Warfarin in AF to prevent stroke 25 Treat BP >/90 to prevent vasc event 700 Mammograms to save 1 cancer death 1,600 Aspirin to prevent AMI/stroke 1,667 Osteoporosis Rx to prevent # Fem > 60 yr 1,945 Regular seat belt use to prevent death 50,000