PNEUMONIA : PROMISE FULFILLED? Regina Berba MD FPSMID

PNEUMONIA : PROMISE FULFILLED? Regina Berba MD FPSMID

Objectives of Lecture Know the quality of current evidence based guidelines on immunization Appreciate the performance of pneumonia vaccines in terns of hard clinical outcomes such as preventing deaths and hospitalization

Streptococcus pneumoniae (the pneumococcus) Pathogen 1,2 Gram-positive diplococcus: first isolated 1881 More than 90 known serotypes Polysaccharide capsule: key virulence factor Reservoir 1,3 Human nasopharynx: children (~20 40%) > adults (~5 10%) Transmission 1 Self-inoculation Respiratory droplets Incubation 1 As short as 1 to 3 days (specific to pneumococcal pneumonia) Kallista Images, Kallista Images, Getty Images 1. Centers for Disease Control and Prevention (CDC). In: Atkinson W et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed., 2nd printing. Public Health Foundation; 2012:233 248. cdc.gov/vaccines/pubs/pinkbook/downloads/pneumo.pdf. Accessed July 10, 2013. 2. World Health Organization. Wkly Epidemiol Rec. 2008;83:373 384. 3. García-Rodríguez JA et al. J Antimicrob Chemother. 2002;50(Suppl S2):59 73.

Pneumococcal Disease Manifestations 1 All-Cause Community-Acquired Pneumonia (CAP) Pneumococcal Pneumonia Invasive Pneumococcal Pneumonia (eg, bacteremic pneumonia) Other Invasive Pneumococcal Disease (eg, bacteremia, meningitis) Other Noninvasive Forms of Pneumococcal Disease (eg, sinusitis, bronchitis) Diagram for illustrative purposes only not drawn to scale 1. World Health Organization. Wkly Epidemiol Rec. 2008;83:373 384.

Pneumococcal Disease Burden in Adults Aged 50 Years: Estimated Annual Health Care Burden of Major Disease Manifestations United States, 2004 1,a Inpatient Pneumonia 302,000 cases 223,000 ED visits 1.7 million hospital days Outpatient Pneumonia 140,000 cases 51,000 ED visits Bacteremia 7,000 cases 61,000 hospital days Meningitis 1,700 cases 19,000 hospital days Diagram for illustrative purposes only not drawn to scale. ED=emergency department. a Based on data from the Centers for Disease Control and Prevention (CDC) Active Bacterial Core surveillance, national health care utilization data, existing literature, and expert panel opinion. 1. Huang SS et al. Vaccine. 2011;29:3398 3412.

The Incidence Rate of Pneumococcal Disease Increases With Age and With Certain Chronic Conditions 1 Incidence Rate of IPD, United States (1999 2000) IPD=invasive pneumococcal disease. 1. Kyaw MH et al. J Infect Dis. 2005;192:377 386. Kyaw MH et al. The influence of chronic illnesses on the incidence of invasive pneumococcal disease in adults. J Infect Dis, 2005, Vol 192, Issue 3, 377 386, by permission of Oxford University Press on behalf of the Infectious Diseases Society of America.

Risk of IPD

Dwindling Vaccine Response with Age

Pneumococcal Vaccines 1 Pneumococcal polysaccharide vaccines (PPVs) Serotype-specific capsular polysaccharides Pneumococcal conjugate vaccines (PCVs) Serotype-specific capsular Serotype-specific polysaccharides linked ( conjugated ) to a protein carrier 1. Grabenstein JD et al. Clin Microbiol Infect. 2012;18(Suppl 5):15 24.

Immune Response to PPVs vs PCVs 1 PPV Legend PCV Ig=immunoglobulin; PCV=pneumococcal conjugate vaccine; PPV=pneumococcal polysaccharide vaccine. 1. Siegrist C-A. Vaccine immunology. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines. 6th ed. Philadelphia, PA: WB Saunders Company; 2013:14 32. Reprinted from Vaccines, 6 th edition, Siegrist C-A, Vaccine Immunology, p14 32, Copyright 2013, with permission from Elsevier.

Serotypes Contained in PCV13 and PPV23 PPV23 contains 23 serotypes, of which 11 are unique PPV23 2 8 9N 10A 11A 12F 15B 17F 20 22F 33F 1 3 4 5 6B 7F 9V 14 18C 19A 19F 23F PCV13 6A PCV13 contains 13 serotypes, of which 1 is unique 1 Serotypes contained in both vaccines Serotypes unique to PPV23 Serotype unique to PCV13 PCV13=13-valent pneumococcal polysaccharide-protein conjugate vaccine; PPV23=23-valent pneumococcal polysaccharide vaccine. 1. PREVNAR 13 [prescribing information]. New York, NY: Pfizer; 2013. PREVNAR 13 (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) is a registered trademark of Pfizer.

What are the recommendations?

PPV 23 Adults 65 years of age and older High risk; chronic cardiovascular and pulmonary disease (including asthma), cigarette smokers and diabetes People without a spleen, undergoing chemotherapy, infected with the AIDS virus There may be occasions where a second dose is given (consult provider) One dose IM or SC

PPV 23

For CANCER Patients When Cancer chemotherapy or other immunosuppressive therapy is being considered, the interval between vaccination and initiation of immunosuppressive therapy should be AT LEAST 2 WEEKS. Vaccination during chemotherapy and radiation therapy should be avoided.

Revaccination with PPV 23 One time revaccination 5 years after 1 st dose for aged 19-64 years with immunocompromised states If 1 st dose given before age 65- revaccinate once at age 65 No further doses if given at or after age 65 years.

IMMUNOCOMPROMISED STATES Patients are recommended to receive both.

PCV 13

BOTH VACCINES

For those uncertain of vaccination status May give PCV 13 and PPV 23 if indicated and no record exists

Contraindications and Precautions Both PPV 23 and PCV 13 Severe allergic reaction after previous dose Precaution for those with moderate to severe acute illness with or without fever.

Efficacy Trials: PPV 23

Efficacy of PPV 23 : RCT

Mortality Benefit

Well conducted RCT: Efficacy of PPV 23

Efficacy of PPV 23

PPV 23 : EVAN Study

EVAN Study

But we need to use the vaccines for them to work.

Rates of Vaccination in the US

TAKE HOME MESSAGES Pneumococcal diseases are serious and associated with significant mortality 1 in every 20 adults who gets pneumococcal pneumonia die. 2 out of every 10 adults who get bacteremia die. 3 out of every 10 adults who get meningitis die.

www.cdc.gov/vaccines ACIP Products

WHEN MEDITATING OVER A DISEASE, I NEVER THINK OF FINDING A REMEDY FOR IT, BUT, INSTEAD, A MEANS OF PREVENTION. LOUIS PASTEUR