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PNEUMOCOCCUS
A Major Etiology of Public Health
Disease
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Definition
Pneumococcal disease is an infection causedby a type of bacteria called Streptococcuspneumoniae
Serious disease most commonly in youngchildren or elderly adults and the
immunosuppresed persons
Often preceded by respiratory viral infection
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Morphology
Nonmotile, facultatively anaerobic , gram-positive,oval to lancet shaped coccus (0.5-1.2um)
Encapsulated coccus growing in pairs (dipcocci) orshort chains
Normal flora to the nasopharynxof healthy people (carriage)
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EPIDEMIOLOGY
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Pneumococcal Types
Pneumococcal types are 6A, 6B, 14, 19F, 19A and 23 F
which causes 50%-60% of infection in infancy and earlychildhood
Types 3, 4, 6B, 9V, 14 and 23F have been the most frequentcauses of bacteremic infections among adults, accountingfor 53% of such illnesses.
Susceptibility to infection may be influenced by geneticconstitution
Types 45 and 46 have been frequent among black goldminers in South America but rare in white persons in thesame area. Also common Melanesian Populations.
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Pneumococcal Infection
Two Types:
1. Due to direct extension- Conjunctivitis, otitis media, sinusitis, acute exacerbations of chronicbronchitis (AECB), pneumonia
2. Invasive Disease
- Meningitis, bacteremia, joint and bone infections, soft tissue infections,peritonitis, cardiac infections
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Pneumococcal Infection
Pneumococcus remains the most common causeof community acquired pneumonia
Until 2000, 100,000-135,000 patients werehospitalized for pneumonia proven to be caused by S
pneumoniae infection in the United States annually.
Incidence in developed countries is estimated to be 1
and 5/1000 persons per year. Worldwide, the most common cause of death due to
pneumococcal disease is pneumonia.
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Pneumococcal Infection
The pneumococcus is the most common cause
of otitis media
Afflicting of children at least once in their first 6
years of life
S. pneumoniae infection is estimated to cause
over 6-7 million cases of otitis media annually.These numbers have likely decreased somewhat
with the advent of universal vaccinations
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Non Invasive Disease
S pneumoniae infection is an important cause of bacterial co-
infection in patients with influenza and can increase the
morbidity and mortality in these patients.
In post mortem studies of lung specimens from patients who
died of H1N1 influenza A, twenty-nine percent of the
specimens showed evidence of bacterial co-infection, with
almost half of being S pneumoniae.
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Invasive Disease
Statistics for 2008 estimated 43,000 (14.3 per
100,000 population) cases of invasive disease
nationally, with 4,400 (1.5 cases per 100,000
population) deaths.
Children younger than 5 years and adults
older than 65 years are two identified age
groups in whom rates of disease and death
are increased
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Invasive Disease
More than half of deaths due to invasive
pneumococcal disease occur in adults with
specific risk factors (age, immunosuppression)
for severe disease.
Such risk factors are an indication for
vaccination.
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Invasive Disease
Pneumococcal meningitis
A sequela of bacteremia or an extension of
infection from the paranasal sinuses or mastoid to
the cranial cavity
Incidence rate of approx. 1.6/100,000 persons per
year
Remains one of the three commonest forms of
bacterial meningitis
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Mortality and Morbidity
WHO estimates that, worldwide, 1.6 million
deaths were caused by pneumococcal disease
in 2005
With 700,000 to 1 million of these occurring in
children younger than 5 years.
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Meningitis
Bacteremia
Pneumonia
Otitis media
Clinicalseve
rity
Incidence
1.6 million people die of pneumococcal disease every
year
0.7 1million are children < 5 years
(most from developing countries)
World Health Organization, 2007
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Conditions interfering with normal clearanceof bacteria predisposes host to pneumococcalinfections
Chronic pulmonary disease Alcoholism
Congestive heart failure
Diabetes mellitus
Chronic kidney disease
Splenic dysfunction or splenectomy
Immunosuppresed persons
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Countries with highest pneumococcal incidence rate in children
under five years
of age, 2000
0 1000 2000 3000 4000 5000 6000 7000
Sudan
Chad
Malawi
Namibia
Kenya
Botswana
Zambia
Swaziland
Zimbabwe
Central African Republic
Lesotho
incidence rate per 100000
Data Source: WHO/IVB, July 2009
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Streptococcus pneumoniae incidence rate
per 100,000 children under five years of age, 2000
Date of slide: 03 August 2009
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Mortality rate* per 100,000 children under five years of age due to
Streptococcus pneumoniae, 2000
Date of slide: 03 August 2009
10-
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Global Streptococcus pneumoniae cases in
children under five years of age
Top 10 countries, 2000Total= 14.5 million cases, 66% in 10 countries
0 0.5 1 1.5 2 2.5 3 3.5 4
Philippines
Kenya
DR Congo
Ethiopia
Indonesia
Bangladesh
Pakistan
Nigeria
China
India
Millions
Data Source: WHO/IVB, July 2009
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PATHOPHYSIOLOGY
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Colonization and Carrier State
In the first years of life, rates of pneumococcal carriageare high
In children, pneumococcal carriage can be up to 12
distinct serotypes
Pneumococcal carriage rates decline with age
Homotypic anticapsular antibody - body reaction aftercolonization of a given pneumococcal. Reduces thelikelihood of being colonized with the same homotypicstrain.
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Pathogenesis
Colonization of the human nasopharynx may
occur on the day of birth - the type acquired
usually being that of the mother
Injury to any region of the respiratory
epithelium may disturb the relationship
between host and parasite and be followed by
clinical illness
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Pathogenesis
Pathogenesis primarily due to host response
to infection
Three Classes of Virulence Factors:
A. Colonization and migration (spreading) B. Tissue destruction
C. Phagocytic survival
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Pathogenesis
Cellular components:
Complex polysaccharide capsule: Antiphagocytic
Encapsulated (smooth) strains are virulent
Nonencapsulated (rough) strains are avirulent
Type-specific anticapsular antibodies are protective
Capsular polysaccharides are soluble (a.k.a., specific solublesubstances) and free polysaccharides can bind opsonins and
further inhibit phagocytosis
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Pneumococcal colonization: adherence to host cells (nasopharynx) andreplication
Migration (spreading)
organisms may gain access to areas of the upper and/or lowerrespiratory tracts (sinuses, bronchi, eustachian tubes) by direct
extension
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Under normal conditions in a healthy host, anatomic and ciliaryclearance mechanisms prevent clinical infection. However,
clearance may be inhibited by chronic (smoking, allergies,bronchitis) or acute (viral infection, allergies) factors, which canlead to infection
Conjunctivitis, otitis media, sinusitis, Acute exacerbations ofchronic bronchitis (AECB), pneumonia
Alternatively, pneumococci may reach normally sterile areas,such as the blood, peritoneum, cerebrospinal fluid, or joint
fluid, by hematogenous spread after mucosal invasion
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inflammatory response: S pneumoniae cell wall componentsand capsule activate the alternative complement pathway;
antibodies to the cell wall polysaccharides activate the classiccomplement pathway
In the absence of previously acquired serotype-specificantibodies, clinically apparent infection is likely to occur.
Meningitis, bacteremia, joint and bone infections, soft tissueinfections, peritonitis, cardiac infections
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Immune response
Naturally acquired immunity: Type-specific
anticapsular immunity
Artificially acquired immunity: Immunization
via polyvalent vaccine prophylaxis
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CLINICAL MANIFESTATIONS
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Non-Invasive
Conjunctivitis - bilateral and purulent
Otitis Media - usually accompanied by fever and pain
Sinusitis - preceded by a viral infection followed by the
development of a purulent discharge and cough
Acute exacerbations of chronic bronchitis - shortness ofbreath, increased production and/or purulence of sputum,
increased sputum tenacity, cough
Pneumonia - may be preceded by a viral illness that is
followed by an acute onset of high fever
often withrigors, cough productive of rust-colored sputum, pleuritic
pain, exertional dyspnea, tachypnea, tachycardia, sweats,
malaise, and fatigue
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Invasive
Bacteremia- most common manifestation of invasivepneumococcal disease; most cases resolve spontaneously
Meningitis nonspecific and nuerologic signs andsymptoms
Joint and bone infections Septic arthritis (4%) ankles and knees
Osteomyelitis (20%) femur and humerus (children),vertebra (adult)
Soft tissue infections - uncommon Peritonitis - abdominal pain, anorexia, emesis, diarrhea
Cardiac infections - rare; endocarditis, pericarditis
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DIAGNOSIS
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Diagnosis
Two points to remember:
1. Treatment can be started without
determining the microbiologic agent in
uncomplicated, nonsevere, community-
acquired pneumonia
2. Efforts to identify the agent are important
when the disease are more severe and when
the dia nosis of neumonia is not clearl
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Diagnosis
Essentials of Diagnosis
Productive cough, fever, rigors, dyspnea, early
pleuritic chest pain
Consolidating lobar pneumonia on chestradiograph
Gram-positive diplococci on Gram stain of
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Diagnosis
Diagnosis requires isolation of the organism in
culture, although the Gram stain appearance
of sputum can be suggestive
Sputum and blood cultures can be used. It is
positive in 60% and 25% of cases
A good-quality sputum sample shows gram-
positive diplococci
A rapid urinary antigen test for S. pneumoniae,
can assist with early diagnosis in adults
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Diagnosis
Nonspecific findings:
Elevated PMN count >15,000/L
Leukopenia in 10% of cases a poor
prognostic sign
Elevated values in liver function tests
Anemia, low serum albumin levels,hyponatremia, and elevated serum cratinine
levels in 20-30% of patients
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Treatment
Initial antimicrobial therapy for pneumonia is
empiric
Uncomplicated pneumococcal pneumonia
caused by penicillin-susceptible strains of
pneumococcus may be treated on an
outpatient basis with amoxicillin, 750 mg
orally twice daily for 710 days
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TREATMENT
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Treatment
Initial antimicrobial therapy for pneumonia is
empiric
Uncomplicated pneumococcal pneumonia
caused by penicillin-susceptible strains of
pneumococcus may be treated on an
outpatient basis with amoxicillin, 750 mg
orally twice daily for 710 days
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Treatment
For penicillin-allergic patients, alternatives are
azithromycin, clarithromycin, doxycycline,
levofloxacin and moxifloxacin
Monitor for clinical response (eg, less cough,
defervescence within 23 days) because
pneumococci have become increasinglyresistant to penicillin and the second-line
agents.
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Treatment
For hospitalized patients:
Parenteral therapy is generally recommended
at least until there has been clinical
improvement. Aqueous penicillin G, 2 million
units intravenously every 4 hours, or
ceftriaxone, 1 g intravenously every 24 hours,
is effective for strains that are not highlypenicillin-resistant The total duration of
therapy is not well defined, but 1014 days is
standard.
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Prevention
Pneumococcal polysacharride vaccine
PPV contains 25 g of capsular polysaccharide
from 23 pneumococcal serotypes that cause
invasive disease
The vaccine is cost effective among individuals
over the age of 65 years for prevention of
bacteremia.
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Prevention
Target Groups for PPV
all immunocompetent individuals age 65 or
greater
Younger patients that put them at high risk for
invasive pneumococcal disease
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Prevention
Clinical Risk Groups
1. Asplenia or splenic dysfunction
2. Chronic respiratory disease
3. Chronic heart disease
4. Chronic kidney disease
5. Chronic liver disease6. Diabetes mellitus
7. Others - cerebrospinal fluid leaks, individuals
in long-term care facilities, alcoholism,
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Prevention
The efficacy of pneumococcal vaccine in
immunosuppressed patients is less certain
Present recommendations include vaccination
of individuals with human immunodeficiency
virus (HIV) infection, leukemia, lymphoma,
Hodgkin's disease, multiple myeloma, organtransplantation, or chronic use of
glucocorticoids
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Prevention
Pneumococcal vaccine can be given
simultaneously with other vaccines but should
be administered at a separate site
A single revaccination is appropriate for
individuals over the age of 65 who received
initial vaccination more than 5 years earlier
Revaccination is also recommended forimmunocompromised patients and individuals
with functional or anatomic asplenia.
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Prevention
Pneumococcal Conjugate Vaccine (PCV)
a 7-valent protein-conjugated polysaccharide
vaccine
Valency indicates the number of serotypes
included in the vaccine
Efficacy estimate is 93% against invasive
disease caused by serotypes in the vaccine
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Prevention
Preparations
Prevnar a 7-valent pneumococcal conjugate
Pneumovax a 23-valent polysaccharide
vaccine for persons 2 years and older
Dosages and Schedule of Administration PCV-7 is given as a 0.5-mL IM dose
A total of 4 doses - given at 6, 10, 14 weeks
and 12-15 months
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Efficacy of an 11-valent pneumococcal
conjugate vaccine against radiologically
confirmed pneumonia among children less
than 2 years of age in the Philippines: arandomized, double-blind, placebo-
controlled trial.
RESULT: 22.9% reduction of community-acquired radiologically confirmed pneumonia
in children younger than 2 years of age in the
11-valent tetanus-diphtheria toxoid-
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Prevention
Considerations
High-risk children older than 23 months shouldreceive both PCV-7 and PPV-23
When both are indicated, they should not be givensimultaneously, give 6-8 weeks apart
If splenectomy or immunosuppression can beanticipated, vaccination should be done at least 2
weeks beforehand Contraindicated to those with severe allergic reaction
after a previous dose
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Prevention
Other Prevention Strategies
Prevention of illnesses that predispose
individuals to pneumococcal infections
Influenza vaccination
Improve management and control of diabetes,
HIV infection, heart disease, and lung disease
Smoking cessation
Reduction of antibiotic misuse
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THANK YOU