Risk and Prevention of Pneumococcal Disease in Adults

Transcription

1 Risk and Prevention of Pneumococcal Disease in Adults Athena International Conference Antoni Torres. University of Barcelona 1

2 Pneumococcal pneumonia represents the majority of pneumococcal disease* 1, cases per year, persons 50+, USA Bacteremia Meningitis 1700 cases per year, persons 50+, USA 25% Pneumococcal pneumonia 442,000 cases per year, persons 50+, USA Bacteremic 75% Nonbacteremic *Data are estimates derived from statistics; assumptions based on published literature and expert opinion. Includes both inpatient (i.e., hospitalization) and outpatient pneumococcal pneumonia. IPD=invasive pneumococcal disease. 1. Huang SS, et al. Vaccine. 2011;29: Said MA, et al. PLoS One. 2013;8:e

3 Overall CAP incidence* in Europe Literature review in >15 y.o. patients, 60 Studies Overall annual CAP incidence: 1.07 ( )/1000 person-years CAP incidence in men: 1.22 ( ) CAP incidence in women: 0.93 ( ) Incidence in >65 Years: 14.0 ( ) Incidence in COPD: 22.4 ( ) Incidence in HIV: 12.0 ( ) *All incidences reported as per 1000 Person Years Adapted from: Torres A, et al. Thorax. 2013;68:

4 Streptococcus pneumoniae is the most frequently isolated pathogen in CAP: Europe Frequency of Causative Organisms of CAP in Europe, No pathogen identified Pathogen identified S. pneumoniae H. influenzae Legionella spp Staphylococcus spp M. catarrhalis Gram-negative bacilli M. pneumoniae Chlamydophila spp C. burnetti Viruses Adapted from Welte et al. 1 Data are presented as percentage means of frequency of isolation of the respective pathogens from the studies included. Studies were identified by a literature review of all primary articles reporting studies of the clinical and economic burden of CAP in adults in Europe from January 1990 to December S. pneumoniae: most frequently isolated pathogen in CAP patients within the hospital, ICU, and outpatient settings 1,2 CAP=community-acquired pneumonia; ICU=intensive care unit. 1. Welte T et al, Thorax. 2012;67: Lode HM. Respir Med. 2007;101:

5 CAP: risk factors 5

6 Incidence of CAP in adults increases with age United Kingdom, Spain, A 2 year, prospective, observational cohort study conducted in a large UK teaching hospital trust. The study included 920 patients with CAP; 366 had pneumococcal CAP. 1 Prospective cohort study of Spanish community-dwelling elderly individuals aged 65 years or older (n=11,240). All-cause CAP (hospitalised and outpatient) was a primary study endpoint. All cases were radiographically proved and validated by checking clinical records Bewick T, et al. Thorax. 2012;67: Ochoa-Gondar O, et al. BMC Public Health. 2008;8:222. 6

7 Common medical conditions increase pneumococcal pneumonia risk in adults 1 Data from a retrospective cohort study from 3 large, longitudinal, US health care databases of medical and outpatient pharmacy claims from None Diabetes Chronic heart Smokers Chronic liver Alcoholism Asthma disease disease Chronic lung disease 1. Shea KM, et al. Open Forum Infect Dis. Published online May 8, doi: /ofid/ofu024. 7

8 Multiple underlying medical conditions further increase pneumococcal pneumonia risk in adults 1 Estimated annual incidence of pneumococcal pneumonia in the United States in adults, by number of comorbidities, * Risk for persons with 2 at-risk conditions is similar to that of a high risk patient *Persons aged years, years, and 65 years contributed a total of 49.3 million, 30.6 million, and 11.7 million personyears of observation, respectively. Note: At-risk immunocompetent with 1 selected chronic condition, including alcoholism, asthma, chronic heart disease, chronic liver disease, chronic lung disease, diabetes, neuromuscular/seizure disorders, and smoking. 1. Shea KM, et al. Open Forum Infect Dis. Published online May 8, doi: /ofid/ofu024. 8

9 Comorbidities are significantly more frequent in pneumococcal CAP patients Retrospective, Multicenter Study of Adults ( 18 years) Hospitalized With CAP, Barcelona, Spain, (N=241) 1 P<0.05 P<0.05 Streptococcus pneumoniae was the most frequently detected etiological agent. Pneumococcal CAP was identified in 34% of inpatients. P< Sicras-Mainar A et al. BMC Infect Dis. 2012;12:283. 9

10 Individuals previously diagnosed with CAP experience an increased risk of subsequent CAP 1 The risk of CAP increases with the number of previous CAP episodes, and decreases with time since the last episode of CAP Previous CAP Confirmed by Radiograph During Life Time Since Last CAP Population-based, case-control study conducted on a target population aged >14 yrs (n=859,033). A total of 1336 patients with confirmed CAP were matched to control subjects by age, sex and primary centre over 1 year Almirall J, et al. Eur Respir. 2008;31:

11 Prevention Strategies 11

12 CAP risk management strategies in adults Focus on lifestyle interventions Smoking Cessation Alcohol Reduce consumption Nutrition Dietary advice to ensure good nutritional status Contact with children Avoid contact with children with lower respiratory tract infections Dental Hygiene Ensure regular dental visits Vaccination against influenza and Streptococcus pneumoniae Ensure compliance with guidelines CAP, community-acquired pneumonia. Torres A, et al. Thorax. 2013;68:

13 What is the impact of herd protection on pneumococcal pneumonia? 13

14 Impact of PCV13 Invasive and non-invasive pneumococcal diseases France 2 UK 3 USA 1 Norway 4 Nicaragua 9 Denmark 5 Spain 8 Israel 6 Germany 7 References are available on request.

15 A substantial herd effect on IPD has been observed in countries with established pediatric immunization programs 65 years USA 65 years UK Before PCV13 95% interval estimate After PCV13 Predicted in the absence of PCV13 All PCV7 PCV13 only NVT 58 % Observed vs expected cases of PCV5-type* IPD caused in 65 years ( ). Vaccine coverage: 96% in 2013 ( 1 doses, 2-59 months old). Adapted from Moore et al. 1 IPD incidence corrected for proportion of samples serotyped, missing age, denominator compared with and for trend in total IPD upto Reproduced from Waight et al. 3 *PCV5 serotypes: 1, 3, 5, 7F, 19A. IPD, invasive pneumococcal disease; NIP, national immunization program. 1. Moore M, et al. Lancet Infect Dis. 2015;15: Public Health England. Available from: Accessed 26 March Waight PA, et al. Lancet Infect Dis Mar 19 [Epub ahead of print]. 15

16 A substantial herd effect on IPD and pneumonia has been observed with established pediatric immunization programs Reduction of pneumococcal disease following the introduction of PCV vs Non-invasive pneumonia Admissions to hospital per season * p<0.05; Proportion of hospitalization cases prevented at 54% coverage. 1 Table based on data from Simonsen et al. 1 Rate reduction calculated as average of vs 2 years post-pcv13 ( ). IPD Empyema All-cause pneumonia Rate reduction 32%* 37%* 8% 12%* vs Rate reduction 25%* 13% 4% 2% vs Rate reduction 34%* 29%* 1% 3% Number of cases 12,683 6,464 14, ,893 Despite significant reductions in hospitalization due to all-type non-invasive pneumonia and IPD more than 10 years after the start of pediatric vaccination in US subjects of all ages, there is still considerable number of cases 1,2 IPD=invasive pneumococcal disease; NIP=national immunisation program. 1. Simonsen L, et al. Lancet Respir Med. 2014;2: Pilishvili T, et al. J Infect Dis. 2010;201:

17 Early herd protection effects of a PCV13 infant vaccination programme on adult non-bacteraemic disease Incidence rate per population Pneumococcal CAP PCV7 CAP Additional PCV13 CAP Other CAP and untyped pneomococcal CAP PCV Year 5-year prospective cohort study of adults (n=2321) admitted to two large teaching hospitals in Nottingham, UK, with community acquired pneumonia (CAP). Pneumococcal aetiology was identified in 653 (29.3%) adults. Serotype was determined in 444 (68.0%) Incidence rates of adult pneumococcal pneumonia declined over 5 years in a population with high infant PCV coverage PCV13 infant vaccination was followed by reductions in CAP due to PCV13 serotypes indicating early herd protection effects on adult bacteraemic and non-bacteraemic disease Ped PCV7/PCV13 coverage from 92.1% % Adult 65 + PPV23 from 68.2% % during the study period 1. Rodrigo C, et al. Eur Respir J Mar 18. pii: ERJ [Epub ahead of print] 17

18 Comments Despite clear evidence of a herd effect, there remains a significant burden of disease in adults Herd effect has led to a documented positive impact for IPD in unvaccinated individuals in countries with a pediatric NIP and high vaccine uptake 1-4 Recent studies suggest a possible herd effect on pneumonia in the adult population 5-8 Vaccine-type pneumococcal pneumonia remains a substantial burden in older adults and younger populations with certain medical conditions Herd effects are only observed in countries with high uptake of pediatric vaccination (NIPs, good compliance) 9 IPD=invasive pneumococcal disease; NIP=national immunization program. 1. Moore MR. Presented at: ACIP Meeting; October 23, 2013; Atlanta, GA. 2. Public Health England. Available from: Accessed 26 March Hanna JN, et al. Med J Aust. 2010;193: van der Linden M, et al. Presented at: ICAAC; September 12, 2013; Denver, CO. 5. Griffin MR, et al. N Engl J Med. 2013;369: Sherwin RL, et al. J Infect Dis. 2013;208: Simonsen L, et al. Lancet Respir Med. 2014;2: Rodrigo C, et al. Eur Respir J Mar 18. [Epub ahead of print] 9. Eng P, et al. Int J Gen Med. 2014;7:

19 Pneumococcal Antimicrobial Resistance Is an Ongoing Concern % of Streptococcus pneumoniae isolates in Europe that are intermediate or resistant to: A) Penicillin and B) Macrolides, A B < 1% 1% to < 5% 5% to < 10% 10% to < 25% 25% to < 50% > 50% No data reported or less than 10 isolates Not included Antibiotic-resistant S. pneumoniae is a global problem 2 Throughout Europe there were large intercountry variations in the susceptibility of S. pneumoniae to penicillin or macrolides, ranging from 1% to 40% 3 For serogroup 19, 52% of isolates had decreased susceptibility to penicillins and/or macrolides 3 1. European Centre for Disease Prevention and Control. Proportion of penicillins resistant (R + I) Streptococcus pneumoniae in participating countries in Accessed April Song JH, et al. Vaccine 2012;30: ECDC. Antimicrobial resistance surveillance in Europe Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm, Sweden: ECDC;

20 The CDC Recommends Vaccination as the First Step in Preventing Antimicrobial Resistance 1,2 Vaccination Is the First Step in Preventing Infection and Antimicrobial Resistance Among Hospitalized Adults Give influenza/pneumococcal vaccine to at-risk patients before discharge Get influenza vaccine annually CDC=Centers for Disease Control and Prevention. 1. CDC promotes campaign to prevent antimicrobial resistance in healthcare settings [press release]. Atlanta, GA; Centers for Disease Control and Prevention; March 26, Accessed December 23, European Respiratory Society. European Lung White Book. Chapter Accessed April 17,

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22 Conclusions Vaccine efficacy of PCV13 was: 45.6% (95.2% CI 21.8%-62.5%; p<0.001) for preventing the first episode of VT-CAP 45.0% (95.2% CI 14.2%-65.3%; p=0.007) for preventing the first episode of NB/NI VT-CAP 75.0% (95% CI 41.4%-90.8%; p<0.001) for preventing the first episode of VT-IPD Safety profile was satisfactory and consistent with prior adult experience

23 Recommendations of the Advisory Committee on Immunization Practices (ACIP) Use of PCV 13 and PPV 23 Among Adults Aged 65 Years Pneumococcal vaccine-naïve persons PCV13 at age 65 years 6-12 months* PPSV23 "Both PCV13 and PPSV23 should be administered routinely in series to all adults aged 65 years" Persons who previously received PPSV23 PPSV23 already received at age 65 years PCV13 1 years Persons who previously received PPSV23 before age 65 years PPSV23 already received at age 65 years 1 years PCV13 at age 65 years 5 years 6-12 months* PPSV23 *Minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks; PPSV23 can be given later than 6-12 months after PCV13 if this window is missed. Ref: CDC. MMWR (September 19);63(37):

24 European adult national recommendations for PCV13* Age recommendation At-risk recommendation High risk recommendation No recommendation Ireland Portugal Spain Norway Sweden Finland Estonia Latvia Denmark Lithuania Belarus UK Poland Netherlands Belgium Germany *** Czech Rep. Slovakia France Austria Switzerland** Hungary Slovenia Romania Croatia Serbia B&H Bulgaria Italy Greece Russia Ukraine Turkey CauCAR Israel " the recommendations for pneumococcal immunization can be very complex and vary greatly between European countries in terms of age, risk, and which vaccine should be administered." "the Community Acquired Pneumonia Immunization Trial in Adults [CAPiTA] has the potential to impact future pneumococcal vaccination recommendations" B & H, Boznia and Herzegovina; Czech Rep., Czech Republic. *13-valent pneumococcal conjugate vaccine. **Recommend at-risk > 5 years but not approved by Health Authority. ***National: age-based funded but not recommended. Prevenar 13 is a pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed). Please refer to your country specific Summary of Product Characteristics and official recommendations. European Centre for Disease Control (ECDC). Vaccine Schedule. Available from: Accessed March

25 A new option for prevention of CAP in older adults Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to 17 years of age. Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in adults 18 years of age and the elderly. The use of Prevenar 13 should be determined on the basis of official recommendations taking into consideration the risk of invasive disease and pneumonia in different age groups, underlying comorbidities as well as the variability of serotype epidemiology in different geographical areas. Prevenar 13 Summary of Product Characteristics. 25

26 Summary PCV13 pediatric vaccination is associated with a significant herd effect on IPD, and recent studies have also suggested a possible herd effect on pneumonia The persistent burden of disease of pneumonia remains high in adults Pneumonia is still a leading cause of morbidity and mortality Pneumococcal pneumonia is a preventable disease PCV13 might help to protect against the disease 26

27 Sir William Osler 27

28 The Captain of the Men of Death 28

29 Pneumococcal pneumonia and community-acquired pneumonia 29

30 Streptococcus pneumoniae is a leading cause of CAP, meningitis, and bacteremia1 Organism has a polysaccharide capsule 1,2 Defines the serotype Functions as virulence factor Is a vaccine target At least 90 serotypes of S. pneumoniae have been identified 1,2 Serotypes are not equally pathogenic CAP=community-acquired pneumonia. Image obtained from the website of the Centers for Disease Control and Prevention/Janice Carr. Image #9996. Antibiotic resistance in S. pneumoniae is a global concern 1,2 Serotypes found to be antibiotic resistant include 6A, 6B, 9V, 14, 15A, 19A, 19F, and 23F 3,4 A human pathogen commonly carried in the nasopharynx 1 1. Centers for Disease Control and Prevention. Pneumococcal disease. In: Atkinson W, et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed., second printing. Washington, DC: Public Health Foundation; 2012: Accessed March World Health Organization. Available from: Accessed March Linares J, et al. Clin Microbiol Infect 2010;16: Kim SH, et al. Antimicrob Agents Chemother 2012;56:

31 Microbial etiology of community-acquired pneumonia and its relation to severity *Mixed: Bacteria + virus: 29% out of 208 mixed; atypical + virus: 6%. Etiology (%) of CAP by site of care (1474/3523 patients) in Barcelona. Cillóniz C, et al. Thorax. 2011;66:

32 Morbidity and mortality 32

33 Mortality of patients with CAP has not changed significantly % 12% 12% 11.5% (n=4432)* 1 (n=5837) 2 (n=730) 3 (n=11,332) 4 *Mixed patient populations in different settings and countries 90-day mortality in intensive care unit and ward patients. 1. Fine MJ, et al. JAMA. 1996;275: Feikin DR, et al. Am J Pub Health. 2000;90: Restrepo MI, et al. Chest. 2008;133: Klausen HH et al. Respir Med. 2012;106:

34 CAP exerts a high burden of morbidity and mortality on older adults DENMARK Readmission within Mortality During initial hospitalization Within 30 days of discharge 11.5% 8.6% 12.3% 8.0% 4.7% 7 days 14 days 30 days National registry study on elderly Danish citizens (aged 65 years) with an acute admission in 2009 owing to communityacquired pneumonia (n=11,332) Klausen HH et al. Respir Med. 2012;106:

35 Mortality risk exceeds 10% in older adults hospitalized for CAP 1 When hospitalized for CAP, approximately 1 of 10 patients years may be at risk of death Germany, Analysis of the database of the German programme for quality in healthcare, including data for every hospitalised patient with CAP (n=388,406) during a 2-year period (2005 and 2006) Ewig S, et al. Thorax. 2009;64:

36 Mortality risk of severe pneumococcal pneumonia admitted to ICU 1 Mortality in patients with severe pneumococcal CAP admitted to the ICU reaches 28.8 % 28.8% Prospective analysis of 222 patients ICU admitted in France, to determine risk factors of mortality in these patients for severe S. pneumoniae CAP, in Mongardon N, et al. Critical Care. 2012, 16:R

37 A considerable proportion of patients with CAP require hospitalization CAP=community-acquired pneumonia. 1. Franca SA, et al. Braz J Infect Dis. 2002;6: Lopardo G, et al. Presented at: ISPPD-9; March 9-13, 2014; Hyderabad, India. 3. Jokinen C, et al. Am J Epidemiol. 1993;137: Viegi G, et al. Respir Med. 2006;100: Almirall J, et al. Eur Respir J. 2000;15: British Thoracic Society Standards of Care Committee. Thorax. 2009;64(Suppl III):iii1-iii Nelson JC, et al. Vaccine. 2008;26: