PNEUMOCOCCAL DISEASE: A MAJOR HEALTH THREAT

1. PNEUMOCOCCAL DISEASE: A MAJOR HEALTH THREAT Pneumococcal disease: caused by Streptococcus pneumoniae Pneumococcal disease: a major threat to health Non-invasive diseases (e.g. otitis media, pneumonia) Invasive diseases (e.g. bacteraemia, meningitis) Invasive pneumococcal disease is serious and has a high risk of mortality Groups at high risk include elderly persons, persons with chronic diseases, asplenic patients, immunocompromised patients

2. DISEASES CAUSED BY STREPTOCOCCUS PNEUMONIAE

3. PNEUMOCOCCUS: TRANSMISSION AND COLONISATION

4. PNEUMOCOCCUS: PATHOGENESIS

5. PNEUMOCOCCAL EPIDEMIOLOGY: AT-RISK GROUPS (1) ELDERLY PERSONS Laboratory reports of bacteraemic pneumococcal infection per 100 000 population, by age group, in England and Wales

6. THE OVERLAP BETWEEN PNEUMOCOCCAL PNEUMONIA AND INVASIVE PNEUMOCOCCAL DISEASE

7. PNEUMOCOCCAL DISEASE: PNEUMONIA (4) Complications Bacteraemia in 15-30% of patients with pneumonia1,2 high mortality despite appropriate antibiotic therapy overall case fatality rate 15-20% for pneumococcal bacteraemia higher case fatality rates (30-40%) for elderly persons and other vulnerable groups Spread of pneumococci in the blood to other normally sterile sites can cause other invasive pneumococcal diseases (e.g. meningitis) Empyema (pus in the pleural cavity) in about 2% of cases3

8. PNEUMOCOCCAL DISEASE: MENINGITIS (1) Meningitis Inflammation of the meninges (membranes surrounding the brain) Can be caused by a range of microorganisms, as well as be a manifestation of some non-infectious diseases Pneumococcal meningitis Invasive pneumococcal disease Generally, pneumococci invade the CNS from the blood stream Signs and symptoms1 Early stages: fever, irritability, neck stiffness, drowsiness Later stages: headache, seizures, coma The signs and symptoms are not specific to pneumococcal disease

9. PNEUMOCOCCAL DISEASE: MENINGITIS (2) Pneumococcal meningitis�a high risk of mortality Case-fatality rate about 30% in adults1 Higher (about 55%) in older patients and other vulnerable groups2 Disability among survivors1 Learning disability Hearing loss Blindness Paralysis

10. INTRODUCTION: PNEUMOCOCCAL DISEASE (2)

11. EPIDEMIOLOGY: INVASIVE PNEUMOCOCCAL DISEASE (3) PNEUMOCOCCAL MENINGITIS1,2 Annual incidence 1-2/100 000 persons Higher among young children and elderly persons at least 10 times the incidence among an elderly (�60 years) population than among younger adults (20-29 years of age)2 Case-fatality rates are high about 30% in adults and 6% in children3

12. PNEUMOCOCCAL DISEASE: MEDICAL MANAGEMENT (1) Hospitalisation Often required in high-risk groups and/or in severe forms of pneumococcal disease Sometimes admission to an intensive care unit is necessary Empiric treatment using broad-spectrum antimicrobial agents To cover all possible bacterial aetiological agents To overcome increasing antimicrobial resistance to antibiotics High-cost management

13. PNEUMOCOCCAL DISEASE:A SUMMARY S. pneumoniae A bacterium surrounded by a polysaccharide capsule that protects it from phagocytosis Many different serotypes Pneumococcal disease Invasive pneumococcal disease is serious and has a high risk of mortality Risk factors include old age, chronic illness, asplenia and immunodeficiency Mortality remains high despite appropriate antibiotic therapy S. pneumoniae resistance to antimicrobials is increasing (with concomitant increasing cost of management) Prevention of pneumococcal disease among high-risk groups is a priority

14. PNEUMOCOCCUS: DIVERSITY OF SEROTYPES There are at least 90 different serotypes of S. pneumoniae1,2 Each has a capsule of a different chemical composition Each stimulates the production of a different antibody Only a minority of serotypes cause most cases of human disease 8-10 cause two-thirds of serious pneumococcal infections in adults3

15. PNEUMOCOCCAL VACCINES: ANTIGEN COMPOSITION 23-valent pneumococcal vaccine contains purified capsular polysaccharides derived from 23 S. pneumoniae serotypes1 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A,11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F Serotype coverage2,3 85-90% of serotypes responsible for all cases of invasive pneumococcal disease Vaccine includes major serotypes that have developed antimicrobial resistance Cross protection within some serotypes1 For example, antibody response to serotype 6B protects against serotype 6A, which is not in the vaccine

16. PNEUMOCOCCAL VACCINES: IMMUNE RESPONSE Vaccine stimulates 23 type-specific anti-capsular antibodies1 Antibodies aid the destruction of pneumococci by white blood cells The immune response in most elderly patients � 65 years of age: is as good as that of healthy younger adults1 is variable according to serotypes2 The response is decreased in: immunosuppressed individuals (e.g. patients with leukaemia, lymphoma, multiple myeloma, or AIDS)3 Antibody levels generally last 5 years or more4 Note: it is inappropriate to use 23-valent vaccine in children under 2 years of age, because the immune response in this age group is poor 3

17. PNEUMOCOCCAL VACCINES: OVERVIEW OF EFFECTIVENESS Case-control and indirect cohort studies on the effectiveness of the pneumococcal vaccine in preventing invasive pneumococcal disease

18. PNEUMOCOCCAL VACCINES: CLINICAL EFFECTIVENESS Estimation of effectiveness of pneumococcal vaccination in preventing invasive pneumococcal disease caused by vaccine serotypes US Centers for Disease Control study in 2837 patients (� 5 years old) by underlying illness, 1978-1992

19. PNEUMOCOCCAL DISEASE PREVENTION: VACCINATION RECOMMENDATIONS WHO view (Technical Advisory Group convened by WHO Regional Office for Europe, 1988)1 Pneumococcal vaccination should be recommended for all elderly persons (aged �60-65 years) and for persons of any age at high risk of acquiring pneumococcal infection National recommendations Many countries recommend vaccination for specific at-risk groups or conditions Some countries recommend vaccination for elderly persons aged: �60 years: Belgium, Germany, Iceland �65 years: Denmark, Finland, Norway, Sweden, USA, Canada, New Zealand

20. PNEUMOCOCCAL DISEASE PREVENTION: VACCINATION RECOMMENDATIONS Immunocompromised Cardiopulmonary Nursing Age > Country Asplenia Haematological HIV diabetes, renal Other home 65 years Austria l - - l ** l - - Belgium l l l l l l l *** Denmark l l l l - - l Finland l l l l l - l France l l - l ** l - - Germany l l - l - - - Iceland l l - l l l l *** Ireland l l l l l - - Italy l - l - - - - Luxembourg l l l l l l l *** Netherlands l * * * * - - Norway l l l l l - l Sweden l l l l l - l Switzerland l l l l l - - UK l l l l l - - USA l l l l l l l

21. PNEUMOCOCCAL DISEASE PREVENTION: OPPORTUNITIES FOR VACCINATION

22. PNEUMOCOCCAL DISEASE PREVENTION: OVERALL VACCINATION RATES Pneumococcal vaccination rates in the USA, Canada and western Europe in 1996

23. PNEUMOCOCCAL DISEASE PREVENTION: PHARMACOECONOMICS The cost-effectiveness of vaccination to prevent pneumococcal bacteraemia in persons aged �65 years was recently evaluated in the USA

24. PNEUMOCOCCAL DISEASE: CONCLUSIONS Pneumococcal disease Major cause of morbidity and mortality worldwide Diagnosis not always made and difficult to establish Treatment may be complicated by antibiotic resistance Management can be costly Prevention by vaccination is a priority in populations who are at risk: The elderly Patients with chronic cardiovascular, pulmonary, renal, hepatic and metabolic disorders Patients who are immunocompromised Patients with asplenia