Transcript ภาพนิ่ง 1

Role of vaccination for
chronic airway disease
Piamlarp Sangsayunh,MD
Four Components of COPD
Management
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD
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Education
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Pharmacologic
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Non-pharmacologic
4. Manage exacerbations
Etiology of AECOPD
bacteria
non infectious
virus
bacteria and virus
Management of Stable COPD
Pharmacotherapy: Vaccines
 In COPD patients influenza vaccines can
reduce serious illness (Evidence A).
 Pneumococcal polysaccharide vaccine is
recommended for COPD patients 65 years
and older and for COPD patients younger
than age 65 with an FEV1 < 40% predicted
(Evidence B).
Influenza vaccine
Influenza Virus Strains
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
Type A
 moderate to severe
illness
 all age groups
 humans and other
animals
Type B
 changes less rapidly
than type A
 milder epidemics
 humans only
 primarily affects
children
Influenza Epidemiology

Reservoir
Human, animals (type A only)

Transmission
Respiratory
Probably airborne
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Temporal pattern Peak December - March in
temperate area
May occur earlier or later
Communicability Maximum 1-2 days before to
4-5 days after onset
Influenza Type A Subtypes
• Subtypes of type A determined by hemagglutinin (H)
and neuraminidase (N)= glycoprotein
H
N
Influenza Antigenic Changes
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Antigenic Drift
 Minor change, same subtype
 Caused by point mutations in gene
 May result in epidemic
 Antigenic drift produces new virus strains that may
not be recognized by the body's immune system
Example of antigenic drift
 In 2003-2004, A/Fujian/411/2002-like (H3N2)
virus was dominant
Influenza Antigenic Changes
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Antigenic Shift
 Major change, new subtype
 Caused by exchange of gene segments
 May result in pandemic
Example of antigenic shift
 H2N2 virus circulated in 1957-1967
 H3N2 virus appeared in 1968 and completely replaced
H2N2 virus
Antigenic shift, or reassortment, can
result in novel and highly pathogenic
Influenza Seasonal Trends
Burden of Influenza
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10% to 20% of the population is infected
with influenza virus each year
Average of more than 200,000 excess
hospitalizations each year
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Persons 65 and older and 2 years and
younger at highest risk
Average of 36,000 deaths each year
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Persons 65 and older at highest risk of death
Influenza Associated Pulmonary and Circulatory
Deaths, 1998
Age Group (yrs)
0 – 49
50 – 64
>65
Rate (per 100,000)
0.4 – 0.6
7.5
98.3
Hospitalization Rates for Influenza By Age and
Risk Group*
Age Group
0-11 mos
1-2 yrs
3-4 yrs
5-14 yrs
15-44 yrs
45-64 yrs
>65 yrs
Rate**
Rate**
(high-risk)
(not high-risk)
808
471
231
92
62
318
507
274
72
39
23
16
22
182
* Data from several studies 1972 - 2004
* Hospitalizations per 100,000 population
Influenza Season
Recommended Groups for Vaccination
 Children 6-59 months of age
 Healthy adults 65 years old and older
 Persons 5 – 64 years old at high risk for
complications
 Pregnant women
 Residents of nursing homes
 Household contacts of persons at high risk
for complications
 Health care workers
Influenza: High Risk for Complications


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Birth through 59 months of age
Adults 65 years old and older
Chronic lung disease, asthma
Chronic heart disease
Metabolic diseases, e.g. diabetes
Chronic renal disease
High risk of aspiration
Immunosuppression
Pregnancy
Chronic aspirin therapy: 18 years old and
younger
Why a Yearly Influenza Vaccination

Influenza vaccine expires June 30 each
year

Antibodies wane during the year

Surface antigens drift and shift
What are the influenza vaccine
options this season?
There are two types of influenza vaccine:
 Trivalent inactivated vaccine (TIV) — a vaccine containing killed virus that
is given with a needle, usually in the arm. There are three different kinds of
TIV on the market in the U.S. now.
 The regular trivalent inactivated vaccine that given intramuscularly is
approved for people 6 months of age and older, including healthy
people, those with chronic medical conditions, and pregnant women.
 A “high dose” trivalent inactivated vaccine also given intramuscularly
containing 4 times the amount of antigen as the regular TIV that is
approved for use in people 65 and older. It was introduced in 20092010. to create a stronger immune response. More frequent SE
 An intradermal trivalent inactivated vaccine that is given into the dermal
layer of the skin via a single-dose, prefilled microinjection syringe and
that contains less antigen than the intramuscular TIV formulations. The
intradermal vaccine was approved for use in people 18 through 64 years
of age in 2011.
and
 The Live, Attenuated Intranasal Influenza Vaccine (LAIV) that is given as a
nasal spray and can be used in healthy people* 2-49 years of age who are
not pregnant
Trivalent Inactivated Influenza
Vaccine (TIV) Side Effects


The viruses in the injectable influenza
vaccine are inactivated so they do not
cause influenza.
Minor side effects that can occur include
soreness, redness or swelling at the
injection site, fever (low grade), or aches.
If these problems occur, they begin soon
after vaccination and usually last 1 or 2
days.
Live, Attenuated Influenza
Vaccine (LAIV) Side Effects

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LAIV is made from weakened viruses and does
not cause influenza. The vaccine can cause mild
illness in some people who get it.
In children, minor side effects can include runny
nose or mild temporary wheezing. Occasionally
headache, vomiting, muscle aches, or fever have
been reported.
In adults, minor side effects can include runny
nose, headache, sore throat, or cough
People who should NOT be
vaccinated include:

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People who have a severe allergy to chicken eggs (See
below for information about less severe egg allergies.),
People who have had a severe reaction to an influenza
vaccination,
Children younger than 6 months of age (influenza vaccine
is not approved for children in this age group), and
People who have a moderate to severe illness with a
fever (they should wait until they recover to get
vaccinated).
A history of Guillain-Barré Syndrome (GBS) within 6
weeks following receipt of influenza vaccine is a
precaution for the use of influenza vaccine. Such
individuals have a risk of recurrence of GBS with
subsequent vaccination, and if not at high risk of severe
influenza complications should generally not be
vaccinated.
Inactivated Influenza Vaccine Efficacy
 70%
- 90% effective among healthy
persons <65 years of age
 30 - 40% effective among frail elderly
persons
 50% - 60% effective in preventing
hospitalization
 80% effective in preventing death
 Seroprotection is generally obtained within
2 to 3 weeks. The duration of post vaccinal
immunity varies and is usually 6 to 12
months
Northern Hemisphere's 2012-2013
seasonal influenza vaccine



On February 23, 2012 the World Health
Organization (WHO) recommended that the
contain the following three vaccine viruses:
an A/California/7/2009 (H1N1)pdm09-like virus;
an A/Victoria/361/2011 (H3N2)-like virus;
a B/Wisconsin/1/2010-like virus (from the
B/Yamagata lineage of viruses).
While the H1N1 virus is the same, the H3N2 and
B vaccine viruses are different from those that
were selected for the Northern Hemisphere for
the 2011-2012 influenza vaccine.
the Southern Hemisphere seasonal
vaccine for 2011?
On September 29, 2010, in Geneva, Switzerland,
WHO recommended that the Southern
Hemisphere's seasonal influenza vaccine contain
the following three vaccine viruses:
 an A/California/7/2009 (H1N1)-like virus;
 an A/Perth/16/2009 (H3N2)-like virus;* and
 a B/Brisbane/60/2008-like virus.
*Note: A/Wisconsin/15/2009 and
A/Victoria/210/2009 are A/Perth/16/2009-like
viruses.
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Pneumoccocal vaccine
Etiology of AECOPD
bacteria
non infectious
virus
bacteria and virus
S.Pneumoniae is the most prevalent pathogen isolated in patients
with Community Acquired Pneumonia
Pathogen
No. of Patients (%)
Streptococcus pneumoniae
29(11.4)
B. pseudomallei
28 (11.0)
Klebsiella pneumoniae
26(10.2)
Chlamydia pneumoniae
22(8.7)
Hemophilus influenzae
11(4.3)
Mycoplasma pneumoniae
10(3.9)
Staphylococcus aureus
9(3.5)
Escherichia coli
8(3.1)
Streptococcus spp
8(3.1)
Pseudomonas aeruginosa
6(2.4)
M. catarrhalis
2(0.8)
P. fluorescense
1 (0.4)
P. cepacia
1(0.4)
Mixed Reechaipichitkul
infectionsW et al. SE Asian J Tropical Medicine & Public Health 2005;36:156-161.
16(6.3)
31
Who is at Greater Risk for
Pneumococcal Pneumonia

While anyone can get pneumococcal
pneumonia, it usually affects children
under 2 years old and adults, 65 years of
age and older. People with COPD are at
greater risk for developing pneumococcal
pneumonia as are those with other chronic
health conditions such as alcoholism,
heart disease, other types of lung disease,
kidney failure, diabetes, HIV and certain
types of cancer
pneumococcal vaccines
INACTIVATED (KILLED) BACTERIA
PCV7 – associated reductions in IPD
in unvaccinated(USA, 1998–1999)
100
Routine childhood
immunization programs
80
80
Rate (M)
60
Unvaccinated
population
60
94% reduction
38
40
35
65% reduction
23
20
20
*
8
4
3
3
2
2
2
5
5
5
8
2
8
8
2
10
5
4
0
<5
5–17
18–39
40–64
Age Group (Y)
1998 to 1999
2000
2001
2002
2003
Centers for Disease Control and Prevention. MMWR. 2005;54:893-897.
Data from US Active Bacterial Core surveillance program, IPD due to vaccine serotypes.
* P<0.05 for 2003 vs. 1998-1999.
16
?65
23 Pneumococcal Capsular Types
Included in PNEUMOVAX 23
Six serotypes that most frequently cause invasive drug-resistant pneumococcal
infections among children and adults in the United States.
Pneumovax 23
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Prevent Pneumococcal Pneumonia
effective in the prevention of serious
pneumococcal disease:56% to 81%
Protective capsular type-specific antibody
levels generally develop by the third week
following vaccination
T-cell-independent mechanism
pneumococcal polysaccharide vaccine
Who Should Get PPV?
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Adults 65 years of age or older
Anyone over 2 years old who has a chronic illness
such as heart or lung disease, diabetes, alcoholism
or cirrhosis
Anyone over 2 years old who has a disease that
may lower their body's defense to infection, such
as Hodgkin's disease, lymphoma, leukemia, kidney
failure, HIV, AIDS, multiple myeloma, nephrotic
syndrome, damaged or no spleen or organ
transplant
Anyone over 2 years old who is taking a drug or
treatment which can lower their defense against
infection, such as long-term steroids, cancer drugs,
or radiation
Alaskan Natives and some Native American groups.
How Many Doses of PPV Will I Need
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Generally, only one dose of PPV is necessary
(repeat  high risk SE). A second dose is
recommended (5 year later), however, for
the following groups:
Anyone 65 years of age or older who got
their first dose before they turned 65, if at
least 5 years has passed since the dose was
given
Anyone who has a damaged or no spleen,
sickle cell disease, HIV, AIDS, cancer,
leukemia, lymphoma, multiple myeloma,
kidney failure, nephrotic syndrome, an organ
or bone marrow transplant, or who is taking
medication that may lower their immunity,
such as chemotherapy or long-term steroids
What Are the Risks Associated with
PPV?

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PPV is a safe vaccine with few reported
serious side effects. Approximately half of the
people who get PPV, report mild side effects
such as redness or pain at the injection site.
Less than 1% report developing a fever,
muscle aches or more serious, local
reactions.
Severe allergic reactions have been reported,
but are rare. Remember, however, that there
is always a slight risk of serious injury or
death when you take ANY medication or
vaccine, and while PPV is safe, it is no
exception to this rule
Use With Other Vaccines

administered at the same time as
influenza vaccine (by separate injection in
the other arm) without an increase in side
effects or decreased antibody response to
either vaccine.
Timing of Vaccination
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at least two weeks before elective
splenectomy
at least two weeks prior to the initiation of
immunosuppressive therapy
asymptomatic or symptomatic HIV
infection should be vaccinated as soon as
possible after their diagnosis is confirmed
New PPV
What is a polysaccharideconjugate vaccine?
A polysaccharide (PS) is chemically linked
(conjugated) to a protein carrier
PS
PROTEIN
CONJUGATE
T-cell dependent B-cell
response to the Conjugate
Plasma-cell
prioducing IgG
T-helper-cell
B-cell
Memory B-cell
Immune response to
polysaccaride-conjugates (PCV)
Plasma cells
Protective threshold
GMC
GMC
Plasma
cells
0
Memory cells
PCV
+
T-cell–
B-cell
Response
Plasma Cells
Memory Cells
4W
?
Time
4W
3y
Time
Memor
ycells
Plasma Cells
+
Memory Cells
Booster
Comparison of Conjugate vs
Polysaccharide Vaccines
Conjugate
Vaccine
Yes
Polysaccharide
Vaccine
No
Immune memory
Yes
No
Lack of hypo-responsiveness
Yes
No
Booster effect
Yes
No
Persistence of protection due to
booster effect
Reduction of nasopharyngeal
carriage of bacteria
Yes
No
Yes
No
Herd immunity
Yes
No
Property
T-cell dependent immune response
Chanputthiveth U., Update on Pediatric Infectious Disease , Bangkok: PIDST; 2010, p.56-59
Study design 004: Noninferiority
PPV23-naïve adults
Enrollment
Stratification
Study Arms
PCV13 (n = 417)
Subject
Characteristics
• PPSV23 naïve
• US
Age
60–64 y
Age
50–59 y
PCV13 (n = 403)
1 Month
OPA GMT Ratio PCV13 subjects 50–59
vs 60–64 years
PCV13, Age 60–64 y
PCV13, Age 50–59 y
1.4 (146:104)
1
Primary Objective
Results
1.0 (91:93)
3
• Noninferiority criteria met
for all serotypes between
the 2 age groups
4
1.4 (2833:2062)
5
1.4 (269:199)
6A
*
1.7 (4328:2593)
1.6 (3212:1984)
6B
• Response to 9 of 13
serotypes significantly
greater for 50–59 y vs 60–
64 y
1.4 (1520:1120)
7F
1.5 (1726:1164)
9V
1.6 (957:612)
14
– Response to serotype
6A also significantly
higher
1.1 (1939:1726)
18C
1.4 (956:682)
19A
1.2 (599:517)
19F
1.3 (494:375)
23F
0.0
1.0
2.0
Study design 004: Noninferiority
PPV23-naïve adults
Enrollment
Stratification
Study Arms
PCV13 (n = 417)
Subject
Characteristics
• PPSV23 naïve
• US
Age
60–64 y
PPV23 (n = 414)
Age
50–59 y
PCV13 (n = 403)
1 Month
OPA GMT ratio PCV13 / PPV23 in naïve 6064 year old subjects
PPSV23 higher
PCV13 higher
Primary Objective
Results
1.4 (146:104)
1
1.1 (93:85)
3
• Noninferiority criteria met
for all serotypes
1.6 (2062:1295)
4
1.2 (199:162)
5
• >4-fold rise for 6A*
– 88.5% for PCV13
– 49.3% for PPSV23
12.1 (2593:213)
2.8 (1120:405)
7F
2.9 (1164:407)
9V
• Superior response for
8 of 12 serotypes in
common
0.9 (612:692)
14
• Superior response
for 6A
18C
1.9 (1726:925)
19A
1.9 (682:352)
1.0 (517:539)
19F
23F
0.0
1.0
*
2.5 (1984:788)
6B
Secondary Objective
Results
6A
2.0
For specific GMT ratio and values, click on a serotype.
*Serotype 6A is not contained in PPSV23.
GMT, geometric mean titer; OPA, opsonophagocytosis assay.
3.0
4.0
5.0 8.0
5.2 (375:72)
12.0
Study design 3005:
pre-immunized with PPV23 adults aged >70 yrs (US and Sweden)
Enrollment
Study Arms
• Age > 70 yrs
• preimmunized with PPV23
(≥5 years)
PPSV23 (n = 924)
PCV13 (n = 463)
N = 924
Age > 70 Years
PPSV23 (n = 473)
5 yrs
1 Month
Result : Study 3005: pre-immunized with PPV23; single vaccination
Comparison of OPA GMT in subjects >70 yrs; preimmunized PPV23 receivig
Prevnar13 *vs. PPV23
*
Significant difference
OPA GMT
*
*
*
*
*
*
*
*
Serotypes
Prevnar 13 demonstrated statistically significant higher immune
response (OPA GMT) in 10 common serotypes compared with PPV23
Prevnar13 LPD - CDS: 4.0-7.0
*
*
FINISH