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)

• Pathogen1,2

– Gram-positive diplococcus: first isolated 1881

– More than 90 known serotypes

– Polysaccharide capsule: key virulence factor

• Reservoir1,3

– Human nasopharynx: children (~20–40%) > adults (~5–10%)

• Transmission1

– Self-inoculation

– Respiratory droplets

• Incubation1

– As short as 1 to 3 days (specific to pneumococcal pneumonia)

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.

Kallista Images, Kallista Images, Getty Images

1. World Health Organization. Wkly Epidemiol Rec. 2008;83:373–384.

All-Cause Community-Acquired

Pneumonia (CAP)

Pneumococcal

Pneumonia

Other Noninvasive Forms of

Pneumococcal Disease

(eg, sinusitis, bronchitis)

Other Invasive

Pneumococcal Disease(eg, bacteremia, meningitis)

Diagram for illustrative purposes only – not drawn to scale

Invasive

Pneumococcal

Pneumonia (eg, bacteremic

pneumonia)

Pneumococcal Disease Manifestations1

Pneumococcal Disease Burden in Adults Aged ≥50 Years: Estimated Annual Health Care Burden of Major Disease

Manifestations — United States, 20041,a

Diagram for illustrative purposes only – not drawn to scale. ED=emergency department.aBased 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.

Outpatient

Pneumonia140,000 cases

51,000 ED visits

Inpatient Pneumonia302,000 cases

223,000 ED visits

1.7 million hospital days

Bacteremia7,000 cases

61,000 hospital days

Meningitis1,700 cases

19,000 hospital

days

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.

The Incidence Rate of Pneumococcal Disease Increases With Age and With Certain Chronic Conditions1

Risk of IPD

Dwindling Vaccine Response with Age

Pneumococcal Vaccines1

Pneumococcal polysaccharide vaccines (PPVs)

Serotype-specific capsular

polysaccharides

1. Grabenstein JD et al. Clin Microbiol Infect. 2012;18(Suppl 5):15–24.

Pneumococcal conjugate

vaccines (PCVs) Serotype-specific capsular

Serotype-specific

polysaccharides linked (“conjugated”)

to a protein carrier

Immune Response to PPVs vs PCVs1

LegendPPV

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, 6th edition, Siegrist C-A, Vaccine Immunology, p14–32, Copyright 2013, with permission from Elsevier.

Serotypes Contained in PCV13 and PPV23

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.

Serotypes contained in both vaccines Serotypes unique to PPV23 Serotype unique to PCV13

PCV13

PPV23

1

33F2

3 4 5

6A

6B 7F

8 9N

9V

10A 11A 12F

14

15B 17F

18C 19A 19F

20 22F

23F

PPV23 contains 23 serotypes, of which 11 are unique

PCV13 contains 13 serotypes, of which 1 is unique1

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

SCIM or

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 1st dose for aged 19-64 years with immunocompromised states

• If 1st 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