La patologia pneumococcica nell’adulto

1. La patologia pneumococcica nell’adulto Francesco Blasi Dipartimento Fisiopatologia e Trapianti Università degli Studi di Milano

2. Nasal cavity Eustachian tube Nasopharynx Pharynx Larynx Trachea Bronchitis Lungs Pneumococcal bacteria cause disease when they spread beyond the nasopharynx S. pneumoniae Colonisation Meningitis Upper respiratory tract infections Sinusitis Otitis media Invasive disease Lower respiratory tract infections Pneumonia Bacteraemia/ septicaemia Parapneumonic empyema

3. “Pneumococcalparadise”

4. Streptococcus pneumoniae causes a spectrum of invasive and non-invasive disease Vaccination drivers Severity Deaths Invasive Pneumococcal Disease Hospitalisation Costs Volume of cases Economic costs Antibiotic use and resistance Adapted from Melegaro et al. J Infection 2006, 52(1):37–48. Silfverdal et al. Vaccine 2009; 27: 1601–1608. WHO. The global burden of disease. 2008. O’Brien et al. Lancet 2009;374:893–902.

5. The impact of IPD in the EU 4.3 per 100.000 (2009)

6. The impact of Invasive Pneumococcal Disease

7. Age is the first risk-factor: highest incidence and mortality rates of IPD at extremes of age Cases Deaths Incidence of IPD and associated mortality rates (USA, 2009)1 • Centers for Disease Control and Prevention. 2010. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2009. Available at: http://www.cdc.gov/abcs/reports-findings/surv-reports.html [accessed May 2012]

8. IPD incidence is increasing and will continue to risewith an increasing elderly population • The population aged over 65 is increasing at twice the rate of the younger population, and cases of IPD are higher in this population 1 Number of isolates expressing serotypes included in conjugate vaccines causing invasive infection in adults in Portugal (2006–2008) Isolates presenting both erythromycin resistance and penicillin non-susceptibility (EPNSP) are represented by closed black bars. Penicillin non-susceptible isolates (PNSP) are indicated by dark hatched bars. Erythromycin resistant isolates (ERSP) are indicated by light hatched bars. Isolates susceptible to both penicillin and erythromycin are represented by white open bars. • Stupka JE et al. Aging health, 2009; 5(6): 763-774 • Aguiar SI et al. Clina Microbiol Infect 2008; 14: 835–843

9. PPV23 serotypes continue to circulate despiteefforts to increase vaccination coverage After the initiation of PPV23 campaigns in England serotypes contained in the vaccine remained stable or increased in the elderly population2 Incidence of IPD by age for vaccine and non-vaccine serotypes from 1998/99 to 2009/102 • Andrews NJ et al. Vaccine, 2012 article in press

10. I sierotipi circolanti negliultra50enni in Italia Schito GC, et al. GIMMOC Vol. XV Q4, 2011.

11. Also Co-morbidities are highly associated with Pneumococcal Disease

12. Patients with chronic illnesses are a major target group for pneumococcal vaccination Age-Specific Incidence of IPD in Healthy Adults (Aged ≥18 years) vsAdults With Chronic Illnesses, United States, 1999–2000 • Kyaw M et al. J Infect Dis. 2005;192(3):377-386.

13. IPD risk increases in patientswith co-morbidities ODIN study: distribution of IPD patients according to the presence of ≥1 co-morbidity 2010 to 2011 * *includes presence of immunosuppression, HIV infection/AIDS, other immunodeficiencies, cancer or chronic renal disease Data from an interim analysis. Study was a prospective, active, hospital-based surveillance of all culture-confirmed IPD in adults ≥18 years, performed in 7 Spanish hospitals (August 2010-June 2011) • Polverino et al. ECCMID poster presentation, 2012

14. IPD and risk of death is higherin patients with co-morbidities • Patients with certain conditions are associated with an increased risk of contracting, and dying from IPD1 • In a recent Swedish study, IPD case records were reviewed to determine the prevalence of IPD among patients with selected diagnoses1 *Significantly lower relative risk (RR) to die respectively to get IPD among asthma patients. The risk to die remained significantly lower after correcting for age, sex and co-morbidity **Significantly higher RR to get IPD or to die within 30 days from culture, respectively, for a patient with this risk factor compared to all patients without this risk factor • Backhaus E et al. ISPPD poster 2012.

15. Pathophysiologicalinteractionsbetween influenza and bacterialrespiratorypathogens

16. Pathophysiologicalinteractionsbetween influenza and bacterialrespiratorypathogens

18. Antibiotico-resistenza degli pneumococchi circolanti • Su un totale di 105 S. pneumoniae compresi in uno studio microbiologico in Italia, l’incidenza di ceppi pneumococcici che veicolano uno o più tratti di resistenza è pari al 65,7% (1) Resistenza di S. pneumoniae ai macrolidi in EU (2) Most non-susceptible isolates belong to few serogroups, especially serogroups 1, 19, 7 and 3 1. Schito GC, et al. GIMMOC Vol. XV Q 4, 2011. 2. EARSS 2010

19. Pneumonia – Incidence and Mortality • Increasingincidencefrom age 50 years11 • Mortalityvery high • Outpatients (1–2%)11 • Higher in hospitalizedpatients (10–20%)11 • Highestin patientsadmitted to the ICU (up to 50%)11 1) Jokinen C et al. Am J Epidemiol. 1993;137(9):977-988. 2) Viegi G et al. Respir Med. 2006;100(1):46-55. 3) Rossi, PG et al Int J Tuberc Lung Dis 2004; 8:528; 4) Almirall J et al. Eur Respir J. 2000;15(4):757-763. 5) Gutierrez f et al J infect 2006; 53:166-174 6)Ochoa-Gondar et al BMC Public Health 2008; 8: 222 7( Trotter CL et al. Emerg Infect Dis. 2008;14(5):727-733. 8) Schnoor M et al. J Infect. 2007;55(3):233-239. 9) Froes F et al Rev Port Pneumol 2003; 187 10) Ewig S, et al. Thorax. 2009;169:910-914. 11) Welte T. Thorax 2010..

20. A Considerable Proportion of Patients with CAP Require Hospitalization • Jokinen C, et al. Am J Epidemiol. 1993;137:977–988. • Viegi G, et al. Respir Med. 2006;100:46–55. • Almirall J, et al. EurRespir J. 2000;15:757–763. • British Thoracic Society Standards of Care Committee. Thorax. 2001;56 (suppl 4):IV1-IV64. • Nelson JC, et al. Vaccine. 2008;26:4947–4954.

21. Significant direct costsassociated with community acquired pneumonia (CAP) • Hospitalisation costs1 • US • $4 million per 100’000 individuals • Europe • $0.4-1.3 million per 100’000 individuals • 90% of total costs Total direct treatment costs of CAP are largely due to the cost of hospitalisations and the elderly account for a disproportionate share of costs2 • Lode HM, Respiratory Medicine (2007) 101, 1864-1873 • Niederman et al. Clinical therapeutics Vol. 20, N°. 4, 1998

22. Socioeconomic impact of pneumonia in EU is relevant • Europe, pneumonia costs ~€ 10.1 billion annually • inpatient care accounting for € 5.7 billion • outpatient care accounting for € 0.5 billion • drugs accounting for € 0.2 billion • Indirect costs of lost work days amount to € 3.6 billion Pneumonia. In: European lung white book. 2 edn. Sheffield, UK: European Respiratory Society/European Lung Foundation. 2003:55e65. http://www.european-lung-foundation.org/index.php?id=155

23. PNEUMONIA DEATH RATES IN EUROPE (Source www.who.int/whosis/) Rate / 100,000

24. CAP in theElderly Ewig S et al. Thorax 2009; 64: 1092-9

25. CAP incidence is increasing and will continue to risewith an increasing elderly population The population aged over 65 is increasing at twice the rate of the younger population1 Incidence of pneumonia in the older population is four times that of younger populations1 The incidence of CAP in Europe varies by country, age and gender. incidence increases sharply with age1 Mortality amongst hospitalized CAP patients: 520%2 • Stupka JE et al. Aging health, 2009; 5(6): 763-774 • Welte T et al. Thorax, 2012; 67: 71–79 • Rudolph D et al. Antimicrobial Agents and Chemo, 2011; 55(10): 4915–4917

26. CAP Hospitalization Rate/1000 inhabitants in Portugal (2000-2009) CAP Adult Hospitalization (2000-2009): CAP hospitalization / 1.000 inhabitants Internamento/1000h/ano Ano/período Global 65+ 75+  28,4% Admissions CAP/ 1000 inhabitants 2000-2009 Froes F, Diniz A, Mesquita M, Serrado M, Nunes B. Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009. EurRespir J erj02167-2011

27. Pathogens in CAP (using Bartlett criteria): Data from the German CAPNETZ Welte. Internist 2005;260:93

28. Pneumococcal vs.non-pneumococcal CAP • Pneumococcal CAP is associated with a more severe disease course than non-pneumococcal CAP.1 • Significantly more pneumococcal CAP patients required:1 • hospitalization • mechanically ventilation • oxygen insufflation CURB scores on admission Clinical course Pneumococcal CAP Non-pneumococcal CAP Outcome • Pletz MW et al. Pneumologie, 2012; 66: 470–475

29. Hazard-Ratio for different CRB-65-Classes in 2006 22% 20% 18% 16% CRB-65=0 14% CRB-65=1 12% CRB-65=2 HR 10% CRB-65=3 8% CRB-65=4 6% 4% 2% 0% 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 Hospital Stay (days) Hospital Mortality 2006Mortalityduringcourse of hospitalstay

30. La PolmonitePneumococcicaBatteriemica • Lo pneumococco è l’agente eziologico più frequentemente in causa nei pazienti CAP ricoverati in terapia intensiva (2) • Emocolture positive si ritrovano fino al 20-30% dei casi di polmonite pneumococcica (3) • Il case fatality rate per batteriemia pneumococcica può raggiungere il 15-20% negli adulti e il 30-40% nei pazienti anziani, nonostante una terapia antibiotica appropriata e la terapia intensiva (1) 2. Chiou CC. Severe Pneumococcal pneumonia: new strategies for management. CurrOpinCrit Care 2006; 12: 470-476. 3. Spindler C. Prognostic score systems and community acquiredbacteraemicpneumococcal pneumonia. Eur Respir J 2006; 28: 816-823. WHO weekly epidemiological record, no. 42, 17 October 2008. http://www.who.int/wer/2008/wer8342.pdf.

31. S. pneumoniaeeithertriggerspneumonia orpneumoniafollowedbybacteraemia and sepsis A Serotype 19 S. pneumoniae Day 1 Day 2 Day 4 B Serotype 2/3 S. pneumoniae Day1 Day 2 Day 3 Day 4 Henken S, WelteT AAC 2010;54(8):3155-60

32. Overall CAP incidence is also higherin patients with certain conditions The higher the number of underlying diseases, the higher was the risk of CAP1 • Schnoor M et al. Epidemiol Infect, 2007;135:1389–1397

33. “Despite multiple studies conducted during > 30 years, the efficacy and effectiveness of PPV in children and adults remain poorly defined and the subject of controversy.” “There is a need for more efficacious conjugate vaccine covering the majority of pneumococcal serotypes that cause serious diseases in older children and adults worldwide and that are responsible for resistance to commonly used antimicrobial drugs” “WHO supports the ongoing efforts to develop such products” PPV-23 WHO Position Paper WHO position paper on 23-valent pneumococcal polysaccharide vaccine, 2008

34. Current situation • Current situation amongst European adults: • Burden of pneumococcal disease increases at the extremes of age, with older patients (aged 50 onwards) having a higher incidence and mortality from pneumococcal disease • IPDs occur more frequently and have a greater mortality in patients with certain chronic illnesses and other co-morbidities • Some serotypes are more virulent than others • CAP will increase with an aging population and will continue to represent a significant clinical and economic burden

35. Innovation - research