risk and prevention of pneumococcal diseases among patients in critical care setup current evidence...
TRANSCRIPT
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, 97-120.
(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
Invasive pneumococcal disease
Pneumococcal pneumonia
Meningitis, arthritis pleuritis etc.
Non-bacteremic pneumococcal pneumonia
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
RISK OF DECOMPENSATION OF THE UNDERLYING DISEASE
AND INCREASED RISK OF SEVERE PNEUMOCOCCAL DISEASE
Cardiovascular
disease
Pulmonary
diseaseDiabetes Liver cirrhosis
(7) CDC. Recommendations of the ACIP. Prevention of pneumococcal disease. MMWR 1997; 46 (N° RR-8): 1-24
Renal
disease
Chronic pulmonary diseases
Risk factors that lead to chronic inflammation
GenesHereditary deficiency of the protein Alpha1-antitrypsin (AAT)
Exposure to particlesTobacco smokeOccupational dusts and chemicalsIndoor air pollution from heating
and cooking in poorly vented dwellingOutdoor air pollution
OthersLung growth and developmentOxidative stressGenderAgeRespiratory infectionsSocioeconomic statusNutritionCo-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
(22) Moe H Kyaw. The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults. JID 2005;192:377-86
0
50
100
150
200
250
18-34 35-49 50-64 65-79 ≥ 80
Age, Years
IPD
/ 10
0,0
00
pe
rso
ns
Chronic lung disease Healthy
Figure 4: Age-specific incidence of Invasive Pneumococcal Disease in healthy adults versus patients with Chronic lung disease.
Adapted from Kyaw and al, 2005
233.4
71.2
COPD patients enter into a vicious circle
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
Bacterial product
Airway epithelial injury Bacterial colonization
impaired ciliated cell
clearance mechanism
Inflammatory
responseProgression
of COPD
Increased
elastolytic activity
Altered elastase-
Anti-elastase balance
Initiating factors:
Smoking, Chronic bronchitis, Childhood respiratory disease…
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 AssociationNational Heart Lung and Blood InstituteWorld 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 yrsRevaccination
3 years after previous dose for children with chronic renal disease who will be ≤10 yrs at time of revaccinationAlso recommended for other dialysis patients, provided 5 yrs have elapsed since first dose
RationaleChronic renal failure patients are prone for pneumonia≥75 % patients have an adequate response to the vaccineIn 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 vaccinationPneumococcal 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
(33) Butler JC et al. Pneumococcal Polysaccharide vaccine efficacy. An evaluation of current recommendations. JAMA 1993;270
Adapted from Butler and al, 1993.
8473 6977
6575
0
10
20
30
40
50
60
70
80
90
100
Vaccin
e e
ffic
acy
Immunocompetent,Person ≥ 65 years
Diabetes mellitus
Coronary vascular disease
Chronic pulmonary disease
Anatomic asplenia
Congestive heart failure
Figure:
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.
Pneumococcal polysaccharide vaccine is effective in preventing community-acquired pneumonia (CAP) in COPD patients
(34) Alfageme I, Vazquez R, Reyes N et al. Clinical efficacyof anti-pneumococcal vaccination in patients with COPD. Thorax 2006;61;189-195
Figure : Cumulative proportion of patients <65 years without pneumonia during the follow up period.
3 cases for vaccinated persons16 cases for unvaccinated persons
Figure : Cumulative proportion of patient with severe COPD without pneumonia during the follow up period.
12 cases for 132 vaccinated persons20 cases on 114 unvaccinated persons
0 200 400 600 800 1000 1200 1400
Time (days)
vaccinated = 91 control = 116
Log rank = 6.68
P= .0097
10.95
0.90
0.85
0.80
0.750.70
Adapted from Alfageme, 2006
Cu
mu
lati
ve p
rop
ort
ion
of
pat
ien
ts w
ith
ou
t p
neu
mo
nia
0 200 400 600 800 1000 1200 1400 1600
Time (days)
vaccinated = 132 control = 114
1
0.95
0.90
0.85
0.80
0.75
0.70
Log rank = 3.85
P = 0.049
Adapted from Alfageme, 2006
Cu
mu
lati
ve p
rop
ort
ion
of
pat
ien
ts w
ith
ou
t p
neu
mo
nia
76% efficacy in patients <65 years old
48% efficacy in patients with severe COPD
Pneumococcal Polysaccharide vaccine is even more effective in patients
under 65 with severe COPD: 91% efficacy
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 16-
fold 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
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
(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.
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
MethodologyRetrospective cohort study in US & multivariate model - Cost-effectiveness ratio per Quality-Adjusted Life-Year gainedN = 1,898 with chronic lung disease diagnosis2 yearsVaccination with a polysaccharide23-valent vaccineDirect medical costs
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 single-dose 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!