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”

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”

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

• 1068 patients admitted to 3 hospitals• 9% mortality at 30 days

Pneumonia Severity : CURB 65

Lim Thorax 2008

Pneumococcal disease and age

Case control study Atlanta, Baltimore, Ontario228 cases of Invasive pneumococcal disease Excluded immunosuppressed inc cancer

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)

Risks of Pneumococcal disease

Nuorti New Eng J Med 2001

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

Toffee apple

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

Polysaccharide vaccine (23 valent)Pneumovax II

Conjugated polysaccharide vaccinePrevanar (13 valent)

£8.32

£49.10 (x 3)

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

Pneumococcal vaccine timelines

• 1977 14 valent polysaccharide vaccine• 1983 current 23 valent polysaccharide 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

Effectiveness of pneumococcal vaccine

0

50

100

150

200

250

300

350

2005 2006 2007 2008 2009 2010 2011 2012

Public Health England

Isolation of PCV-7 pneumococcal strains in those age <2yr

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

Invasive pneumococcal disease vs pneumonia

Pneumococcal bacteraemia and outcome of pneumonia

• 125 subjects with bacteremic • 1,847 subjects without

Bordon Chest 2008

Time to achieve clinical stabilityTime to dischargeProbability of dying

• 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)

25 studies 18 RCTs with 64,852 subjects; 7 non-RCTs with 62,294 subjects)

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

Duration of protection from pneumococcal polysaccharide vaccine

Shapiro New Eng J Med 1991

Pneumococcal antibody levels

Effectiveness of pneumococcal vaccine

0

50

100

150

200

250

300

350

2005 2006 2007 2008 2009 2010 2011 2012

Public Health England

Isolation of PCV-7 pneumococcal strains in those age <2yr

Herd effectiveness of pneumococcal vaccine

0200400600800

100012001400160018002000

2005 2006 2007 2008 2009 2010 2011 2012

Public Health England

Isolation of PCV-7 pneumococcal strains in those age >5yr

Emergence of non PCV-7 pneumococcal strains

0500

10001500200025003000350040004500

2005 2006 2007 2008 2009 2010 2011 2012

Public Health England

Isolation of non- PCV-7 pneumococcal strains in those age >5yr

Pneumococcal promiscuity

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

Death from pneumonia in metal working occupations 1930-1963

Death from pneumonia in metal working occupations 1979-1990

Pneumococcal and unspecified lobar pneumonia (ICD 481)

Bronchopneumonia (ICD 481)

Other pneumonias (ICD 480, 482-3, 486)

Death from pneumonia in metal working occupations 1991-2000

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 ?

Iron and welding

• Iron facilitates bacterial growth• Iron increases inflammation • Iron is toxic to macrophages

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

• 75,000 welders in the UK• 40-50 hospital admissions pa because of fume• 2 deaths pa

Source : HSE

Welding and pneumonia

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.

• 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

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