Pneumococcal Disease - Epidemiology & Resistance

Pneumococcal Disease
Epidemiology, Drug resistance
and prevention
By.A.Arputha Selvaraj APMP IIM Calcutta

Estimated Annual
Disease Burden Worldwide
 Pneumococcal infections are a major cause of morbidity and
mortality worldwide
 Streptococcus pneumoniae is the #1 cause of bacterial
pneumonia and a leading cause of otitis media
 Pneumococcal infections cause >1 million annual deaths
worldwide
 Most deaths occur in developing countries
 Even in developed countries, invasive pneumococcal disease carries
high mortality in certain population groups (ie, elderly people,
especially those living in institutions, and patients with chronic organ
failure, diabetes, nephrotic syndrome, and immunodeficiencies)
Adapted from World Health Organization. Weekly Epidemiological Record. 2003;78(14):97-120; Beers MH, et al. The Merck Manual
of Diagnosis and Therapy. 18th edition. 2006.

The Primary Causes of Vaccine-Preventable
Deaths in All Age Groups Worldwide
Hib = Haemophilus influenzae type b.
WHO Official Mortality Rates, 2003, cited in and adapted from Global Alliance for Vaccines & Immunization. Speeding access to new, life-
saving vaccines: GAVI’s pneumococcal and rotavirus ADIPs. Available at:
http://www.who.int/vaccine_research/about/gvrf/Levine_Orin.pdf. Accessed October 23, 2006. Used with permission.
Vaccine-Preventable Deaths by Cause (WHO data), June 2003
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
<5 Years of Age ≥5 Years of Age Total
NumberofDeaths
Pneumococci
Measles
Hepatitis B
Rotavirus
Hib
Pertussis
Tetanus
Yellow Fever
Meningitis AC
Diphtheria
Polio

Estimated Annual Burden of Invasive
Pneumococcal Disease in Defined Populations
in the US According to Age, 1998–2005 (CDC
Data)
CDC = Centers for Disease Control and Prevention.
Adapted from Active Bacterial Core Surveillance Report, 1998. Available at: http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu98.pdf. Accessed
October 24, 2006; ABCs Report, 2001. Available at: http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu01.pdf. Accessed October 24, 2006; ABCs
Report, 2005. Available at: http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu05prelim.pdf. Accessed October 24, 2006.
0
50
100
150
200
250
<1 1 2–4 5–17 18–34 35–49 50–64 65+ Total
Age (years)
1998 (N = 17,383,935)
2001 (N = 22,479,308)
2005 (N = 27,419,898)
Casesper100,000

Epidemiology of Pneumococcal
Pneumonia (US CDC Data)
 Total cases per year
 500,000
 Hospitalized cases per year
 175,000
 Case fatality rate
 5%–7% (higher in elderly)
 Responsible for:
 Up to 36% of adult community-acquired pneumonia
 Up to 50% of adult hospital-acquired pneumonia
Adapted from CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases: The Pink Book. 9th edition; CDC. MMWR.
2005;54(RR-05):1-9.

Bacteremia (US CDC Data)
 Cases per year
 >50,000
 20% (up to 60% in elderly)
 Incidence in patients with pneumococcal
pneumonia
 25%–30%
Adapted from CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases: The Pink Book. 9th edition.

Meningitis (US CDC Data)
 Cases per year
 3,000–6,000
 ~30% (up to 80% in elderly)
 Responsible for 13%–19% of all cases of
bacterial meningitis
Adapted from CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases: The Pink Book. 9th edition.

Temporal Incidence Patterns of
Invasive Pneumococcal Disease
 Pneumococcal infections occur year-round, with seasonal peaks in winter
Monthly Rates of Invasive Pneumococcal Disease in Adults and Children in
Defined Populations in Australia, 2004 (N = 2,375) Based on a Surveillance
Study
Adapted from Roche P, et al. Commun Dis Intell. 2006;30(1):80-92. Used with permission.
Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec
400
350
300
250
200
150
100
50
0
Notifications
Month
Total Cases
<5 years
≥5 years

Incidence of Invasive Pneumococcal
Disease in Viral Season (US CDC
Data)
Viral season
MeanWeeklyFrequency
ofPneumococcalDisease
*P < 0.05; †
P < 0.01.
CDC ABCs = Centers for Disease Control and Prevention Active Bacterial Core Surveillance.
Adapted from Talbot TR, et al. Am J Med. 2005;118(3):285-291. Figure used with permission; McCullers JA. Clin Microbiol Rev. 2006;19(3):571-582.
0
20
15
10
5
25
Early
1995
1995-
1996
1996-
1997
1997-
1998
1998-
1999
1999-
2000
2000-
2001
2001-
2002
Year (July 1–June 30)
†
†
†
†
† †
*
Nonviral season
 Viral respiratory infections increase the risk of pneumococcal disease
Surveillance Study Conducted in Tennessee, US by CDC
ABCs; Total Population of Surveillance Area N = 2,283,929
†

Populations at Risk of
Pneumococcal Disease
 Certain age groups
 ie, persons ≥65 years of age and young children
 Cigarette smokers
 People living in crowded environments
 People with chronic diseases
 Immunodeficient individuals
 Members of certain racial and ethnic groups
 ie, African Americans, Alaskan Natives, and American
Indians
Adapted from Whitney CG, et al. Clin Infect Dis. 2001;33:662–675; Ortqvist A, et al. Semin Respir Crit Care Med. 2005;26(6):563-574; Fletcher MA, et
al. Int J Pract. 2006;60(4):450-456; CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases: The Pink Book. 9th edition.

Disease In India

Disease In India
CAP = community-acquired pneumonia.
*Pseudomonas species, Enterobacter species, Citrobacter species, Acinetobacter species.
Adapted from Bansal S, et al. Indian I Chest Dis Allied Sci. 2004;46:17-22. Used with permission.
S
pneum
oniae
K
pneum
oniae
S
aureus
M
pneum
oniae
E
coli
B
eta-hem
olytic
streptococci
O
therG
ram
-negative
bacilli*
0
5
10
15
20
25
30
35
40
%ofIsolates
Microbiologic Diagnoses in Patients >15 Years of Age
Presenting With CAP March 2000–February 2001 at an
Academic Hospital in Shimla, India (n = 70)
Based on a Surveillance Study

Streptococcus pneumoniae:
The Bacterium
 Gram-positive
 Polysaccharide
capsule important
virulence factor
 >90 known capsular
types
 Type-specific
antibody is protective
S pneumoniae and the associated
pneumococcal capsular
polysaccharide
CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases: The Pink
Book. 9th edition; Ho CF, Lin TY. Chang Gung Med J. 2005;28(11):765-772.
Adapted from Jones C. An Acad Bras Cienc. 2005;77(2):293-
324. Epub 2005. Used with permission.

Drug Resistance Complicates
Management of Pneumococcal Disease
 Multidrug-resistant pneumococci are common
and increasing
 Up to 35% of pneumococcal isolates in some areas are
penicillin-resistant
 There are multiple consequences of pneumococcal
antibiotic resistance
 Treatment failures
 The need for expensive alternative antimicrobial agents
 Prolonged hospitalization
 Increased medical costs
Adapted from Whitney CG, et al. N Engl J Med. 2000;343:1917-1924; Whitney CG, et al. Clin Infect Dis. 2001;33:662–675;
Schrag SJ, et al. Resistant Pneumococcal Infections. WHO, 2001; CDC. MMWR. 1997;46(RR-08):1-24.

Factors Associated With
Pneumococcal Antibiotic Resistance
 Young age
 Setting: day-care centers and hospitals
 HIV infection
 Certain infective serotypes (6, 9, 14, 19, and 23)
 Aspects of community/individual antibiotic use:
 Ongoing, recent, repeated, frequent, and/or
prophylactic use
 Recent use of trimethoprim-sulfa
Adapted from Kristinsson KG. Microb Drug Resist. 1997;3(2):117-123; Schrag SJ, et al. Resistant Pneumococcal Infections. WHO,
2001.

Penicillin Resistance in Asia
ANSORP = Asian Network for Surveillance of Resistant Pathogens; MIC = minimum inhibitory concentrations.
*According to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines for breakpoints.
Adapted from Song JH, et al. Antimicrob Agents Chemother. 2004;48(6):2101-2107.
0
20
40
60
80
100
C
hina
(n
=
111)
Taiw
an
(n
=
57)
K
orea
(n
=
31)
SriLanka
(n
=
42)
Singapore
(n
=
35)
M
alaysia
(n
=
44)
Vietnam
(n
=
64)
Philippines
(n
=
22)
H
ong
K
ong
(n
=
112)
%ofIsolates
Resistant (MIC >2 mg/L) Intermediately resistant (MIC 0.12-1 mg/L)
India
(n
=
77)
SaudiArabia
(n
=
39)
Resistance* to Penicillin of 111 S pneumoniae Isolates in
ANSORP, 2000–2001

Organizations That Have Issued
Guidelines for Pneumococcal
Vaccination
 World Health Organization (International)
 Advisory Committee on Immunization Practices
(US)
 American Thoracic Society
 Canadian Medical Association
 United Kingdom Department of Health
 National Health and Medical Research Council
(Australia)
Adapted from World Health Organization. Weekly Epidemiological Record. 2003;78(14):97-120; Centers for Disease Control
and Prevention. MMWR. 1997;46(RR-08):1–24; National Advisory Committee on Immunization. Canadian Immunization
Guide, 2002; United Kingdom Department of Health: The pneumococcal immunisation programme for older people and risk
groups, 2005; National Health and Medical Research Council: The Australian Immunisation Handbook, 8th Edition, 2003.

Advisory Committee on
Immunization Practices (US)
Recommendations

US ACIP* Recommendations for
Pneumococcal Polysaccharide Vaccination:
Overview of Candidates
 High-risk patients who have not received prior
immunization or whose prior vaccination status is
unknown
 All persons ≥65 years of age
 Persons 2–64 years with underlying medical
conditions
 Immunocompromised persons >2 years of age
*US ACIP=United States Advisory Committee on Immunization Practices.
Adapted from CDC. MMWR. 1997;46(RR-08):1–24.

US ACIP* Recommendations for Pneumococcal
Polysaccharide Vaccination in Persons >2
Years With Underlying Medical Conditions
 Chronic cardiovascular disease
 Chronic pulmonary disease
 Diabetes mellitus
 Alcoholism
 Chronic liver disease
 Cerebrospinal fluid leaks
 Functional or anatomic asplenia

US ACIP* Recommendations for Pneumococcal
Polysaccharide Vaccination in
Immunocompromised Persons ≥2 Years of Age
 HIV† infection
 Leukemia
 Hodgkin’s disease
 Lymphoma
 Multiple myeloma
 Generalized malignancy
 Chronic renal failure
 Nephrotic syndrome
 Immunosuppressive chemotherapy/ Organ or bone marrow
transplant
†
HIV=human immunodeficiency virus.

Pneumococcal Polysaccharide
Vaccination if Vaccination Status Is
Unknown
 The ACIP recommends administration of the
pneumococcal vaccine for all immunocompromised
persons if prior vaccination status is unknown

Pneumococcal Polysaccharide Revaccination
for Immunocompetent Persons
Group Special Considerations
Persons aged >65 years If patient received vaccine ≥5
years previously and was <65
years of age at time of initial
vaccination, revaccinate
Persons 2–64 years with functional or
anatomic asplenia†
If patient is >10 years of age,
administer single revaccination ≥5
years after previous dose
If patient is <10 years of age,
consider revaccination 3 years
after previous dose
†
Including sickle cell disease and splenectomy.

Pneumococcal Polysaccharide Revaccination
for Immunocompromised Persons
Persons ≥2 years of age with:
 HIV infection
 Leukemia, lymphoma, Hodgkin’s
disease, multiple myeloma,
generalized malignancy
 Chronic renal failure, nephrotic
syndrome
 Immunosuppressive
chemotherapy (including long-
term systemic corticosteroids)
 Organ or bone marrow
transplantation
Single revaccination ≥5 years
after previous dose
In patients ≤10 years of age:
single revaccination 3 years after
previous dose

Revaccination of Immunocompetent
Persons
Persons aged >65 years If patient received vaccine ≥5
years previously and was <65
years of age at time of initial
vaccination, revaccinate
Persons 2–64 years with functional or
anatomic asplenia†
If patient is >10 years of age,
administer single revaccination ≥5
If patient is <10 years of age,
consider revaccination 3 years
after previous dose
†
Including sickle cell disease and splenectomy.

Revaccination of
Immunocompromised Persons
Persons ≥2 years of age with:
 HIV infection
 Leukemia, lymphoma, Hodgkin’s
disease, multiple myeloma,
generalized malignancy
 Chronic renal failure, nephrotic
syndrome
 Immunosuppressive chemotherapy
(including long-term systemic
corticosteroids)
 Organ or bone marrow
transplantation
If ≥5 years have elapsed since
previous dose: single
revaccination
In patients ≤10 years of age:
consider single revaccination 3

American Thoracic Society-Guidelines
 23 Valent pneumococcal polysaccharide
vaccine is recommended for persons >65 yr of
age & for those with selected high-risk
concurrent diseases (strong recommendations;
level II evidence)
 Smoking cessation should be a gial for persons
hospitalized with CAP who smoke( Moderate
recommendations, level III evidence)

American Thoracic Society-Guidelines
Contd:
 Smokers who will not quit should also be
vaccinated for both pneumococcal &
influenza ( weak recommendation; level
III evidence)

US Pneumococcal Vaccination Rates
According to CDC* vs. Healthy People 2010
Goals
 Adult vaccination rates in the US in 2002 and 2003 were
far below Healthy People 2010 goals
* Data for persons >65 years of age from US Behavioral Risk Factor Surveillance System, 2003; data for high-risk persons 18-64 years of age from US
National Health Interview Survey, 2002
**Persons with one or more risk factors for pneumococcal disease
Adapted from Centers for Disease Control and Prevention. Healthy People 2010: Immunization and Infectious Diseases. Available at:
http://www.healthypeople.gov/Document/pdf/Volume1/14Immunization.pdf. Accessed February 12, 2007; CDC MMWR. 2005;54(RR-5):1–13; CDC
MMWR. 2004;53(43):1007–1012.
Healthy People
2010 Goal: 90%
Healthy People
2010 Goal: 60%
19.1
64.2
0
10
20
30
40
50
60
70
80
90
100
Individuals
>65 Years of Age
(2003)
High-Risk Individuals**
18-64 Years of Age
(2002)
%ofadultsvaccinated

Efficacy of polyvalent
polysaccharide
Pneumococcal vaccine

Protective Efficacy of 6- and 13-Valent
Vaccines in Healthy Young Males*
*Combined results of 3 controlled clinical studies in 12,000 young adult males, mostly from Malawi and Mozambique, who were randomized to receive
pneumococcal vaccine (containing serotypes 1,3,4,7,8, and 12 in Trial 1 and serotypes 1,2, 3, 4, 6, 7, 8, 9, 12,14, 18,19, and 25 in Trials 2 and 3), Group A
meningococcal vaccine, or saline placebo.
Adapted from Austrian R, et al. Trans Assoc Am Phys. 1976;89(7):184-194.
Protective Efficacy Against Pneumococcal Bacteremic Pneumonia
82.3%
78.5%
76
77
78
79
80
81
82
83
3 Trials of 6-Valent or
13-Valent Vaccine
(N=12,000)
2 Trials of 13-Valent
Vaccine
(N=4,500)
%protectiveefficacy

Combined Protective Efficacy of 6- and 12-
Valent Vaccines in South African Gold
Miners*
*Two separate controlled clinical studies in 4,694 South African gold miners conducted In the 1970s In which subjects were randomized to receive
pneumococcal vaccine (6-valent in one study and 12-valent in the other), Group A meningococcal vaccine, or placebo
**vs meningococcal vaccine and placebo
Protective Efficacy Against Pneumococcal Pneumonia in 2 Separate Trials:
Pneumococcal Pneumonia Cases ≥14 Days After Vaccination
Protective
Efficacy
76%
p<0.001**
Protective
Efficacy
92%
p<0.004**
Trial of 6-Valent Pneumococcal Vaccine Trial of 12-Valent Pneumococcal Vaccine
9.2
1.8
38.1
15.4
38.6
29
0
5
10
15
20
25
30
35
40
45
Pneumococcus
(n=983)
Meningococcus
(n=1051)
Placebo
(n=985)
Pneumococcus
(n=540)
Meningococcus
(n=585)
Placebo
(n=550)
Rate/1,000patients

Protective Efficacy in Prospective Trials
(Meta-Analysis)*
*Meta-analysis of 14 prospective, randomized trials in which the 6-, 12-, 13-, 14-, or 23-valent pneumococcal polysaccharide vaccine was administered to a
total of 48,837 immunocompetent adults.
Note: There was no significance identified in the subgroup of patients >55 years of age, probably due to lack of statistical power.
CI=confidence interval
Adapted from Cornu C, et al. Vaccine. 2001;19(32):4780-4790.
Protective
Efficacy
40%
(CI: 0.60–0.96)
Protective
Efficacy
71%
(CI: 0.2–0.42)
Definite Pneumococcal Pneumonia
(6 Trials)
Presumptive Pneumococcal Pneumonia
(8 Trials)
5.5
22
19
34
0
5
10
15
20
25
30
35
40
Pneumococcal Vaccine
(n=6689)
Control
(n=6441)
Pneumococcal Vaccine
(n=11945)
Control
(n=13714)
rate/1,000patients

Timing of Antibody Response
(Seroconversion)
Antibody titers develop by the third week
following vaccination

Duration of Protection
 Following pneumococcal vaccination, serotype-
specific antibody levels decline after 5–10 years
 A more rapid decline in antibody levels may occur in
some groups (eg, children, the elderly)
 The results of one epidemiologic study suggest that
vaccination may provide protection for at least
9 years after receipt of the initial dose

Indications
 PNEUMOVAX ®
23 is indicated for vaccination
against pneumococcal disease caused by those
pneumococcal types included in the vaccine
 Effectiveness of the vaccine in the prevention of
pneumococcal pneumonia and pneumococcal
bacteremia has been demonstrated in controlled
trials in South Africa and France and in case-
controlled studies
PNEUMOVAX® 23 is a registered trademark of Merck & Co., Inc. Whitehouse Station, NJ, USA

Indications for Immunocompetent
Persons
 Vaccination with PNEUMOVAX ®
23 is recommended
for selected immunocompetent individuals as follows:
 Routine vaccination for persons aged ≥50 years
 Persons aged ≥2 years with chronic cardiovascular
disease, chronic pulmonary disease, diabetes mellitus,
alcoholism, chronic liver disease, cerebrospinal fluid
leaks, functional asplenia, or anatomic asplenia
 Persons aged ≥2 years living in special environments or
social settings

Indications for Immunocompromised
Persons
 Vaccination with PNEUMOVAX ®
23 is recommended
for selected immunocompromised persons aged ≥2
years as follows:
 Persons with HIV infection, leukemia, lymphoma,
Hodgkin’s disease, multiple myeloma, generalized
malignancy, chronic renal failure, nephrotic syndrome
 Persons receiving immunosuppressive chemotherapy
(including corticosteroids)
 Persons who have received an organ or bone marrow
transplant

Contraindications
 PNEUMOVAX ®
23 is contraindicated in
individuals who are hypersensitive to any
component of the vaccine
 Epinephrine injection (1:1000) must be available
immediately should an acute anaphylactoid
reaction occur due to any component of the
vaccine

Precautions—General
 If PNEUMOVAX ®
23 is used in persons receiving
immunosuppressive therapy, the expected serum antibody response
may not be obtained and potential impairment of future immune
responses to pneumococcal antigens may occur
 Intradermal administration may cause severe local reactions
 Caution and appropriate care should be exercised in administering
PNEUMOVAX ®
23 to individuals with severely compromised
cardiovascular and/or pulmonary function in whom a systemic
reaction would pose a significant risk
 Any febrile respiratory illness or other active infection is reason for
delaying use of PNEUMOVAX ®
23, except when, in the opinion of the
physician, withholding the agent entails even greater risk
 In patients who require penicillin (or other antibiotic) prophylaxis
against pneumococcal infection, such prophylaxis should not be
discontinued after vaccination with PNEUMOVAX ®
23

Precautions—Special
Populations
Pregnant Women Nursing Mothers
Children
<2 years of age
• It is not known
whether
PNEUMOVAX ®
23
can cause fetal harm
or can affect
reproduction capacity
when administered to
a pregnant woman
• PNEUMOVAX ®
23
should be given to
pregnant women only
if clearly needed
• It is not known
whether
PNEUMOVAX ®
23 is
excreted in human
milk
• Caution should be
exercised when
PNEUMOVAX ®
23 is
administered to a
nursing mother
• PNEUMOVAX ®
23 is
not recommended in
this age group

Adverse Reactions
 In clinical trials and/or postmarketing experience
with PNEUMOVAX ®
23, the following adverse
experiences were reported:
 Injection-site reactions (including soreness,
erythema, warmth, swelling, local induration,
decreased limb mobility, and peripheral edema in
the injected extremity), fever (≤38.8º C/102º F), and
increases in lab values for C-reactive protein
 Cellulitis-like reactions (very rare)

Dosage and Administration
 Inspect product visually for particulate matter and discoloration prior
to administration. PNEUMOVAX ®
23 is a clear, colorless solution
 Withdraw 0.5 mL from the vial using a sterile needle and syringe free
of preservatives, antiseptics, and detergents
 Administer a single 0.5 mL dose of PNEUMOVAX ®
23
subcutaneously or intramuscularly (preferably in the deltoid muscle or
lateral mid-thigh), with appropriate precautions to avoid intravascular
administration
 Use a separate sterile syringe and needle for each individual patient
to prevent transmission of infectious agents from one person to
another
 Store unopened and opened vials at 2°–8° C/35.6°–46.4° F. Use the
vaccine directly as supplied, without dilution or reconstitution. Phenol
0.25% is added as a preservative. Discard all vaccine after the
expiration date

Vaccine Schedule for Special
Populations
 Pneumococcal vaccine should be given at least 2 weeks
before elective splenectomy, if possible
 For patients planning cancer chemotherapy or other
immunosuppressive therapy, the interval between
vaccination and initiation of immunosuppressive therapy
should be at least 2 weeks
 Vaccination during chemotherapy or radiation therapy
should be avoided
 Pneumococcal vaccine may be given several months
following completion of chemotherapy or radiation therapy
for neoplastic disease

Vaccine Schedule for Special
Populations, continued
 In patients with Hodgkin’s disease, immune response to
vaccination may be suboptimal for 2 years or longer after
intensive chemotherapy (with or without radiation)
 For some patients, during the 2 years following the completion
of chemotherapy or other immunosuppressive therapy (with or
without radiation), significant improvement in antibody
response has been observed, particularly as the interval
between the end of treatment and pneumococcal vaccination
increased
 Persons with asymptomatic or symptomatic HIV infection
should be vaccinated as soon as possible after their diagnosis
is confirmed

Use With Other Vaccines
 The ACIP recommends that pneumococcal vaccine be
administered at the same time as influenza vaccine
 Concomitant administration of the pneumococcal and
influenza vaccines does not increase side effects or
decrease the antibody response to either vaccine
 Influenza vaccine is recommended annually for
appropriate populations
 Pneumococcal vaccine is not given annually
ACIP=Advisory Committee on Immunization Practices

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Pneumococcal Disease - Epidemiology & Resistance

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