Transcript Risk and prevention of pneumococcal diseases among

Risk and prevention of
pneumococcal diseases
among patients in critical
care setup
Current evidence and
guidelines…
Table of contents
1.
Review of S. pneumoniae and pneumococcal diseases
2.
Chronic lung disease
3.
Chronic renal disease
4.
Immunosuppressed population
5.
Impact of pneumococcal infections in patients with chronic lung
disease
6.
Vaccine recommendations for patients with chronic lung disease
7.
Pneumococcal vaccination
8.
Health economic benefits of pneumococcal vaccination
Review of S. pneumoniae
and pneumococcal
diseases
Review of S.pneumoniae and pneumococcal
diseases (1/2)
Invasive Pneumococcal Disease (IPD) carries high risk of
mortality (1)
S. pneumoniae is the leading cause of Community-acquired
pneumonia (CAP) (2)
>90 serotypes of S. pneumoniae (3)
8-10 cause two-thirds of serious infections in adults (4)
The infections caused by pneumococci include
pneumococcal pneumonia, bacteremia and meningitis (5)
Review of S.pneumoniae and pneumococcal
diseases (2/2)
Pneumococcal diseases are serious and associated with
significant mortality (6)
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.
(1) World Health Organization. Weekly Epidemiological Record. Pneumococcal vaccines No. 14, 2003, 78, 97120.
(2) Jokinen C, Heiskanen L, Juvonen H et al. Microbial etiology of community-acquired pneumonia in the adult
population of 4 municipalities in eastern Finland. Clin Infect Dis. 2001 Apr 15;32(8):1141-54.
(3) Fedson DS, Musher D. Pneumococcal polysaccharide vaccine. In: Plotkin A, Orenstein WA editors. Vaccines.
4th ed. Philadelphia, USA: WB Saunders Company; 2004. p. 529-88.
(4) Pneumococcal. In: The green book chapter 25. Immunization against infectious disease. London, United
Kingdom Department of Health; 2006.
(5) Musher DM. Streptococcus pneumoniae. In: Mandell G, Bennett JE, Dolin R editors. Principles and practice of
infectious disease. 4th ed. New-York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26.
(6) CDC. Pneumococcal Polysaccharide Vaccine: What you need to know. [Online] 2007; [3 pages]. Available
at: http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-ppv.pdf
Invasive pneumococcal disease
Meningitis, arthritis pleuritis
etc.
Invasive pneumococcal disease
Bacteremic pneumococcal
pneumonia
Pneumococcal pneumonia
Non-bacteremic pneumococcal
pneumonia
Overlap between pneumococcal pneumonia and invasive pneumococcal disease
Adapted from Fedson DS. Pneumococcal vaccination for older
adults—the first 20 years. Drugs Aging 15(suppl 1):21–30, 1999.
Factors predisposing to pneumococcal
disease (1/2)
Age (7)
Chronic illnesses (7)
Functional or anatomical asplenia (7)
Immunodeficiency (7)
Environmental factors (5)
(7) CDC. Recommendations of the ACIP. Prevention of pneumococcal disease. MMWR 1997; 46 (N° RR-8): 1-2
(5) Musher DM. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p.1811-26
Factors predisposing to pneumococcal
disease (2/2)
Focus on Chronic illnesses
Pulmonary
Cardiovascular
Renal
disease
disease
disease
Diabetes
Liver cirrhosis
RISK OF DECOMPENSATION OF THE UNDERLYING DISEASE
AND INCREASED RISK OF SEVERE PNEUMOCOCCAL DISEASE
(7) CDC. Recommendations of the ACIP. Prevention of pneumococcal disease. MMWR 1997; 46 (N° RR-8): 1-24
Chronic pulmonary
diseases
Risk factors that lead to chronic inflammation
Genes
Hereditary deficiency of the protein Alpha1-antitrypsin (AAT)
Exposure to particles
Tobacco smoke
Occupational dusts and chemicals
Indoor air pollution from heating
and cooking in poorly vented dwelling
Outdoor air pollution
Others
Lung growth and development
Oxidative stress
Gender
Age
Respiratory infections
Socioeconomic status
Nutrition
Co-morbidities
(11) Buist S, Pauwels R, and al.Global Initiative for Chronic Obstructive Lung Disease report 2006.
(12) American Lung Association. COPD. [Online], August 2006. Available from: URL: http://www.lungusa.org/site/pp.aspx?c=dvLUK9O0E&b=35020&pritmode=1
Chronic Obstructive Pulmonary Disease (COPD)
A major health problem
According to the WHO:
80 million have moderate to severe COPD
>3 million died of COPD in 2005, ≈5% of all deaths globally
In 2002 COPD was the 5th leading cause of death
Deaths from COPD are projected to increase by >30% in the
next 10 years
COPD expected to be 4th leading cause of death worldwide by
2030
(9) World Health Organization. Chronic respiratory diseases. Burden. [Online]. 2007; [1 page]. Available from: URL: http://www.who.int/ respiratory/copd/burden/en/index.html
Infections have a role on exacerbations in
COPD patients
Bacterial infection is a factor in 70 - 75% of
exacerbations
(15)
up to 60% caused by S.pneumoniae, H. influenzae or M.
catarrhalis
The presence of an upper respiratory tract infection
leads to:
(17)
more severe exacerbation
longer symptom recovery time at exacerbation
(15) Hunter M and King D. COPD: Management of acute exacerbations and chronic stable disease. American Family Physician 2001; Vol 6; number 4; 603-612
(16) Wongsurakiat P and Al. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination. Chest 2004, 125(6): 2011-2020
(17) Jadwiga A. Wedzicha. Role of viruses in exacerbations of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc. Vol 1., 2004, pp 115-120.
Impact of pneumococcal
infections in patients with
COPD
Patients with chronic lung disease are at higher risk
of invasive pneumococcal diseases especially in
the elderly
250
233.4
IPD/ 100,000 persons
Chronic lung disease
Healthy
200
150
100
71.2
50
0
18-34
35-49
50-64
65-79
≥ 80
Age, Years
Figure 4: Age-specific incidence of Invasive Pneumococcal Disease in healthy adults versus patients with Chronic
lung disease.
Adapted from Kyaw and al, 2005
(22) Moe H Kyaw. The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults. JID 2005;192:377-86
COPD patients enter into a vicious circle
Initiating factors:
Smoking, Chronic bronchitis, Childhood respiratory disease…
impaired ciliated cell
clearance mechanism
Airway epithelial injury
Bacterial colonization
Inflammatory
Progression
Bacterial product
of COPD
Altered elastase-
Increased
Anti-elastase balance
elastolytic activity
response
Figure 5: Schematic diagram of the vicious circle hypothesis of the role of bacterial colonization in the progression of COPD.
Adapted from Sanjay, 2000
(8) Salyers AA, Whitt DD. Streptococcus pneumoniae. In: Bacterial Pathogenesis: A Molecular Approach. 2nd ed. Washington, USA: ASM Press; 1994. p. 322-31.
(23) Sanjay Sethi. Bacterial infection and the Pathogenesis of COPD. Chest 2000;117;286-291
Pneumococcal vaccination
recommended
for patients with COPD
Pneumococcal vaccine: Antigen composition
23-valent pneumococcal vaccine contains purified
capsular polysaccharides derived from 23 S.
pneumoniae serotypes
(3, 7)
Serotype coverage
(3, 7)
85-90% of serotypes responsible for all cases of IPD
Vaccine includes major serotypes that have developed
antimicrobial resistance (90%)
(3) Fedson DS, Musher D. In: Plotkin A, Orenstein WA editors. Vaccines. 4th ed. Philadelphia, USA: WB Saunders Company; 2004. p. 529-8
(7) CDC. Prevention of pneumococcal disease. Recommendations of the ACIP. MMWR 1997; 46 (N° RR-8): 1-2
(47) Wagner C. et al. Impact of pneumococcal vaccination on morbidity and mortality of geriatric patients: a case-controlled study. Gerontology 2003; 49:246-250.
Several associations recommend
pneumococcal vaccination: Summary (1/2)
IMA (Indian Medical Association)
ISN (Indian Society of Nephrology)
The ACIP (Advisory Committee on Immunization Practices)
AAFP (American Association of Family Physicians)
ACOG (American College of Obstetricians and Gynecologists)
ACP (American College of Physicians)
ATS (American Thoracic Society)
American Lung Association
National Heart Lung and Blood Institute
World Health Organization (WHO)
All recommend Routine administration of 23 valent
polysaccharide vaccine to all ≥65 yrs, and younger at-risk
individuals
Several associations recommend
pneumococcal vaccination: Summary (2/2)
IAP (Indian Academy of Pediatrics)
AAP (American Academy of Pediatrics)
ACIP (Advisory Committee on Immunization Practices)
All recommend Routine administration of 23 valent
polysaccharide vaccine to all at-risk children ≥2 yrs
Children 24-59 months of age, with a high risk of
Pneumococcal infection can benefit more from a sequential
schedule, i.e. children who have received 4 doses of
Pneumococcal Conjugate Vaccine (7-valent PCV) should get
a single dose of 23-valent PPV 6-8 weeks after the last dose
of PCV
ACIP/ CDC recommends pneumococcal
vaccination*
Condition
Timing
All persons aged ≥65 yr
Repeat in 5 yr
Chronic lung disease
Repeat in 5 yr
(COPD, cystic fibrosis)
Heart disease, Diabetes mellitus
Repeat in 5 yr
Nephrotic syndrome or renal failure
Repeat in 5 yr
Liver disease
Repeat in 5 yr
Splenectomy (functional or anatomic) 2 wk before, if possible; repeat in 5 yr
Organ transplantation
2 wk before, if possible; repeat in 5 yr
Immunosuppressive chemotherapy
2 wk before, if possible; repeat in 5 yr
HIV infection
Repeat in 5 yr
Recurrent pneumococcal infections
Repeat in 5 yr
(7) CDC. Prevention of pneumococcal disease. Recommendations of the ACIP. MMWR 1997; 46 (N° RR-8): 1-24
WHO recommends pneumococcal
vaccination (1,26)
Healthy elderly (over 65 years of age), particularly those
living in institutions
Patients with chronic organ failure, heart, lung, liver or
kidney, diabetes mellitus, alcoholism
Children ≥2 yrs at high risk for disease (splenectomised
children and sickle-cell disease)
Patients with immunodeficiencies particularly those with
functional or anatomical asplenia
Prevention of subsequent pneumococcal infection in
patients recovering from proven or assumed
pneumococcal pneumonia
(1) World Health Organization. Weekly Epidemiological Record. Pneumococcal vaccines.No. 14, 2003, 78, 97-120.
(26) Immunization, Vaccines and Biologicals. Pneumococcal vaccines. [Online] 2003. Available from URL http://www.who.int/vaccines/en/pneumococcus.shtml
Several other associations recommend both
pneumococcal and influenza vaccination
According to the American Thoracic Society (27)
Patients at risk for community-acquired pneumonia should be
vaccinated with both pneumococcal and influenza vaccine.
Vaccines can be given simultaneously but at separate sites of
injection
According to the American Lung Association, the National
Heart Lung and Blood Institute: (12,28)
Pneumococcal and influenza vaccines should be given to
patients with chronic pulmonary conditions and other high risk
groups
(12) American Lung Association. COPD. [Online], August 2006. Available from: URL: http://www.lungusa.org/site/pp.aspx?c=dvLUK9O0E&b=35020&pritmode=1
(27) American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. 2001
(28) National Heart Lung and Blood Institute. COPD. Available at http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_Treatments.html
Several other associations recommend
pneumococcal vaccination
The Indian Medical Association recommends
administration of pneumococcal vaccine in special
circumstances such as:
Chronic Renal Disease
Immunodeficiency conditions
Congenital or acquired asplenia/ splenic dysfunction
HIV infection
Chronic cardiac and pulmonary disease
Cerebrospinal fluids leaks
Diabetes mellitus
Indian Medical Association. http://www.imanational.com/PH0.htm 10-19-2006
Several other associations recommend both
pneumococcal vaccination
IAP recommends Pneumococcal vaccination in all children with :
Sickle cell disease
Nephrotic syndrome on remission, especially those with a previous
episode of peritonitis
Congenital or acquired asplenia/ splenic dysfunction
HIV infection
Chronic cardiac and pulmonary disease
Immunodeficiency conditions
Cerebrospinal fluids leaks
Diabetes mellitus
S. pneumoniae colonizes the throats of upto 91% children of 6
months to 5 years of age
23-valent polysaccharide vaccine is capable of prevention of 85% of
meningitis and bacteremia caused by pneumococcus
A single IM injection is recommended after the age of 2 years with
revaccination every 3-5 years till the age of 10 years
IAP Guidebook on Immunization
Several other associations recommend
pneumococcal vaccination
Indian Society of Nephrology recommends 23 valent
pneumococcal vaccination in patients with chronic renal
disease
Single dose to be given IM or SC to all dialysis patients ≥2 yrs
Revaccination
3 years after previous dose for children with chronic renal disease who
will be ≤10 yrs at time of revaccination
Also recommended for other dialysis patients, provided 5 yrs have
elapsed since first dose
Rationale
Chronic renal failure patients are prone for pneumonia
≥75 % patients have an adequate response to the vaccine
In healthy person antibody titer remain elevated for 5 years and
decrease to pre vaccination level after10 years. But in chronic
renal failure patients, a rapid decline occurs in 6 months to 5
years after vaccination
Pneumococcal vaccine is well tolerated
Indian J Nephrol 2005;15, Supplement 1: S72-S74
Pneumococcal
vaccination
Patients with COPD respond to
pneumococcal and influenza vaccination
PNEUMOCOCCAL POLYSACCHARIDE VACCINATION (31)
The immunogenicity of the pneumococcal polysaccharide
vaccine in patients with bronchopulmonary disease equals that
of healthy controls
INFLUENZA VACCINATION (32)
Following influenza vaccination, COPD patients experience a
significant increase in HI (haemagglutinin) and NI
(neuraminidase) antibody titres which is not significantly
different from that of healthy controls.
(31) Belgian consensus on pneumococcal vaccine. Acta Clin Belg. 1996;51-5:350-6
(32) Tadeusz Plusa, et al. Effect of influenza vaccinations on humoral response in patients with bronchial asthma or chronic obstructive pulmonary disease.
International Congress eries, Options for the Control of Influenza V. Proceedings of the International Conference on Options for the Control of Influenza V. Volume
1263, June 2004, 563-567.
Pneumococcal polysaccharide vaccine provides
good efficacy in preventing pneumococcal infection
in patients with chronic illnesses
100
90
Vaccine efficacy
80
70
75
60
84
73
77
65
69
50
40
30
20
10
0
Immunocompetent,
Person ≥ 65 years
Diabetes
mellitus
Coronary
vascular
disease
Chronic
pulmonary
disease
Anatomic
asplenia
Figure:
Congestive
heart failure
Adapted from Butler and al, 1993.
Reduction of invasive pneumococcal infections in the elderly and other at risk patients.
Indirect cohort analysis for 2,837 patients over the age of 5.
(33) Butler JC et al. Pneumococcal Polysaccharide vaccine efficacy. An evaluation of current recommendations. JAMA 1993;270
Pneumococcal polysaccharide vaccine is effective
in preventing community-acquired pneumonia (CAP)
in COPD patients
48% efficacy in patients
with severe COPD
Cumulative proportion of
patients without pneumonia
Cumulative proportion of
patients without pneumonia
76% efficacy in patients
<65 years old
1
0.95
0.90
0.85
0.80
Log rank = 6.68
0.75
P= .0097
0.70
0
200
400
600
800
1000
1200
1400
1
0.95
0.90
0.85
0.80
Log rank = 3.85
0.75
P = 0.049
0.70
0
200
600
800
1000
1200
1400
1600
Time (days)
Time (days)
vaccinated = 91
400
control = 116
Figure : Cumulative proportion of patients <65 years
without pneumonia during the follow up period.
3 cases for vaccinated persons
16 cases for unvaccinated persons
vaccinated = 132
control = 114
Figure : Cumulative proportion of patient with severe COPD
without pneumonia during the follow up period.
12 cases for 132 vaccinated persons
20 cases on 114 unvaccinated persons
Adapted from Alfageme, 2006
Adapted from Alfageme, 2006
Pneumococcal Polysaccharide vaccine is even more effective in patients
under 65 with severe COPD: 91% efficacy
(34) Alfageme I, Vazquez R, Reyes N et al. Clinical efficacyof anti-pneumococcal vaccination in patients with COPD. Thorax 2006;61;189-195
Chronic renal disease
Chronic Kidney Disease Carries a Big Risk
for Pneumococcal Disease
Pneumonia remains a major cause of morbidity and mortality in
patients with renal disease
Rates of pneumonia during the first year of hemodialysis have
increased gradually from 24.8 admissions/100 patient-years at risk
in 1991 to 30.6 admissions/100 patient-years at risk in 2001.1
S pneumoniae is responsible for up to 53% of reported pneumonia
cases in dialysis patients.34
Mortality rates after pneumonia in dialysis patients: up to 14- to 16fold greater mortality compared with the general population
The Use of Vaccines in Adult Patients With Renal Disease Am J Kidney Dis 46:997-1011.
The Value of Pneumococcal Vaccination in
Chronic Kidney Disease
Infectious disease is the second most common cause of death in
late-stage chronic kidney disease (CKD/ ESRD) patients
Centers with vaccination protocols have demonstrated reduced
infection rates and resultant decreased morbidity and mortality
It could be extrapolated from this that widespread vaccination would
reduce the total cost of ESRD patient care, and potentially improve
patient well-being
Vaccination appears to be underutilized in CKD patients, and it is a
readily available intervention to improve outcomes
Kausz A; Pahari D Semin Dial 2004 Jan-Feb;17(1):9-11
Benefits of pneumococcal
vaccination:
pharmaco-economic perspective
Pneumococcal vaccination of elderly with
chronic lung disease is cost-saving
Over the 2 yr outcome period, pneumococcal vaccination is
associated with
Reduction p-value
Reduction in the number of hospitalizations for pneumonia
43%
.005
Reduction in the risk of death
29%
.008
 Cumulative 2-year net cost-saving associated with pneumococcal vaccination:
US$294 per vaccinee
 In every scenario, vaccination was found to be a cost-saving strategy
Methodology
Retrospective cohort study in US & multivariate model - Cost-effectiveness
ratio per Quality-Adjusted Life-Year gained
N = 1,898 with chronic lung disease diagnosis
2 years
Vaccination with a polysaccharide23-valent vaccine
Direct medical costs
(37) Nichol K L. and al. The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease, Arch
Intern Med 1999; 159:2437-2442.
Pneumococcal polysaccharide vaccination
is safe
There are no contraindications to pneumococcal vaccination
(except a severe reaction to a previous dose)
(3)
The most frequently reported adverse events are fever, and
local reaction at the injection site.
(42)
Severe systemic reactions are very rare
(42)
(3) Fedson and Musher. In: Vaccines, 4th ed. 2004
(42) Sanofi Pasteur, Pneumo 23 product prescribing information. June 2005
Pneumo23™
Composition and presentation
Each 0.5 ml dose contains
25 µg of each of the 23 pneumococcal capsular polysaccharide types
Isotonic saline
Phenol preservative
is presented as a sterile solution in a singledose pre-filled syringe or multidose vial.
can be administered intramuscularly or
subcutaneously
(42) Sanofi Pasteur, Pneumo 23 product prescribing information. June 2005
CONCLUSION
Patients with Chronic Lung Diseases as well as Chronic
Kidney Diseases are at increased risk for pneumococcal and
influenza infections
Influenza and pneumococcal infections can be effectively
prevented using available vaccines
Vaccines are cost-effective, safe, and efficacious
Thank You!