PNEUMOCOCCAL VACCINE

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PNEUMOCOCCAL VACCINE

• Charisse De Los Reyes, M.D.

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HISTORY

• PNEUMOCOCCUS - First identified in 1881 by
  Pasteur
• More than 80 serotypes of pneumococci described
  by 1940
• Central role of Ab in host defense against
  extracellular organisms was first described for
  Pneumococcus
• First recognition that Ab directed to capsular
  polysaccharide of a bacteria could be protective
  was shown for the Pneumococcus

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HISTORY OF PNEUMOCOCCAL VACCINE

• Efforts to develop effective pneumococcal
  vaccines began as early as 1911
• Advent of PCN in 1940s, decline in interest in
  pneumococcal vaccine
• Deaths despite ABx tx, thus, efforts made again
  in 1960s
• 1st pneumococcal vaccine licensed in US in 1977
• 1st conjugate pneumococcal vaccine icensed in 2000

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PNEUMOCOCCUS (Streptococcus pneumoniae)

• Vaccine covering 23 serotypes
• Common inhabitant of the respi tract (nasopharynx
  of 5-70 healthy adults)
• Asymptomatic carriage
• Vary with age, environment of URTI
• 5-10 of adults w/o children
• 27-58 of residents in schools/orphanages
• 50-60 of service personnel
• Duration of carriage varies is generally longer
  in children than in adults

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MICROBIOLOGY

• Lancet-shaped, G() diplococci, alpha-hemolytic
• Catalase(-) requires source of catalase to grow
  on agar plates e.g. blood, generate H2O2
• Optochin-sensitive
• Some are encapsulated ( surface composed of
  complex polysaccharides)
• Capsular polysaccharides are the primary basis
  for pathogenicity antigenic basis for serotypes

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SPUTUM FR PNEUMOCOCCAL PNA
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MICROBIOLOGY

• 90 serotypes
• Type-specific Ab to capsular polysaccharide is
  protective
• These Abs complement interact to opsonize
  pneumococci
• Antibodies to some pneumococcal capsular
  polysaccharides may cross-react w related types

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MICROBIOLOGY

• Only a few serotypes produce the majority of
  pneumococcal infections
• 10 most common serotypes account for 62 of
  invasive disease worldwide
• In the US, 7 most common serotypes isolated fr
  blood/CSF of children lt 6yrs account for 80
  infections account for only 50 isolates

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PATHOGENESIS

• CAPSULE
• Surface capsular poysaccharide
• Basis for serotyping (90 diff serotypes)
• 6, 14, 18, 19, 23 60-80 of infxns
• Major antiphagocytic surface element
• ADHERENCE
• Exports proteins which noncovalently link to
  human cell carbohydrate or rPAF

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ADHERENCE
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• INVASION
• Invade cells poorly, up to 10 x less than other
  streptococci
• Promoted by cell wall, adhesins, cytotoxin
  pneumolysin
• Inhibited by capsular polysaccharide
• CHOLINE cell wall component ligand for rPAF
  mimicry activation of host cells to upregulate
  rPAF
• Endocytosis ? Transocytosis
• 1 study showed adenovirus-infected cells in
  vitro increased binding uptake of S. pneumoniae
  

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• REGULATORY MECHANISMS
• Use many regulatory mechanisms for surface
  changes in response to new environment
• Secrete pneumolysin pore formation promotes
  intraalveolar replication, penetration
  dissemination of pneumococci

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• 5. HOST INFLAMMATORY RESPONSE
• Cell wall impt virulence determinant (induce
  strong IL-1 response exceeding that of endotoxin
  by at least 10 fold)
• Teichoic acid Lipoteichoic acid of cell wall
  contribute strongly to host defense response
• Activate complement (alternative pathway)
• Bind CRP
• Activate procoagulant activity on endothelial
  surface
• Induce production of cytokines, nitric oxide, and
  PAF
• Initiate the influx of neutrophils

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PNEUMOCOCCAL DISEASE

• Immunologic mechanism that allows disease to
  occur in carriers is poorly understood
• Lung dse is a major predisposing factor
• MAJOR CLINICAL SYNDROMES
• Pneumonia
• Bacteremia
• Meningitis

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PNEUMOCOCCAL DISEASE

• PNEUMONIA
• Among adults, most common
• Account for 36 of adult CAP 50 HAP
• Abrupt onset, fever, chills, pleuritic chest
  pain, produc. cough, SOB, tachypnea, hypoxia,
  tachycardia, malaise
• Common bacterial complication of influenza
  measles
• CFR is 5-7, higher in elderly

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COMPLICATIONS OF PNEUMOCOCCAL PNA
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PNEUMOCOCCAL DISEASE

• 2. BACTEREMIA
• Occurs in 25-30 w pneumococcal PNA
• CFR 20 up to 60 in elderly
• Rates higher in extremes of age
• Asplenia fulminant course
• 3. MENINGITIS
• 13-19 of all bacterial meningitis in US
• CFR 30, up to 80 among elderly
• Neurologic sequelae common among survivors

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PNEUMOCOCCAL DISEASE IN CHILDREN

• BACTEREMIA(w/o a known infxn site)
• Most common CP in lt2 yrs
• 70 of invasive dse in this age
• MENINGITIS
• leading cause of bacterial meningitis (W decline
  of invasive Hib) in lt5yrs
• PNEUMONIA
• 12-16 of invasive pneumococcal dse lt2yrs
• OTITIS MEDIA
• 28-55 of middle ear aspirates

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BURDEN OF PNEUMOCOCCAL DISEASE IN
CHILDRENPrior to routine use of pneumococcal
conjugate vaccine
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CHILDREN AT INCREASED RISK OF INVASIVE
PNEUMOCOCCAL DISEASE

• Functional/anatomic asplenia, esp. sickle cell
  disease
• HIV infection
• Alaska Native, African American, American Indian
• Childcare attendance
• Cochlear implant

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LAB DIAGNOSIS

• Definitive diagnosis isolation of organism fr
  blood or other normally sterile body sites
• Capsular polysaccharide Ags in body fluids
• Gram stain
• Quelleng reaction

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RESISTANCE
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MEDICAL MANAGEMENT
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PNEUMOCOCCAL DISEASE EPIDEMIOILOGY
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TYPES OF PNEUMOCOCCAL VACCINE

• Pneumococcal conjugate vaccine (7-valent)
• Prevnar
• Dosing 0.5mL IM
• Pneumococcal polysaccharide vaccine (23-valent)
• Pneumovax
• Dosing0.5mL IM/SC

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USE OF PNEUMOCOCCAL VACCINE
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1. PPV7 (PREVNAR)

• Purified capsular polysaccharide of 7 serotypes
  (4, 9V, 14, 19F, 23F, 18C, 6B)
• Vaccine serotypes account for 86 of bacteremia,
  83 of meningitis 65 of AOM among lt6 yrs

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PPV7 (PREVNAR)

• IMMUNOGENICITY VACCINE EFFICACY
• After 4 doses, gt90 of healthy infants develop Ab
  to all 7 serotypes
• Reduced invasive dse caused by vaccine serotypes
  by 97 by all serotypes by 89
• Reduced clinically diagnosed PNA by 11,
  xray-confirmed PNA by 73
• Duration of protection unknown

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PCV7 (PREVNAR)

• Infants 2-6 months 4 doses at 2, 4, 6
  12-15mos.
• Previously Unvaccinated
• 7-11months 3 doses, 2 doses 4 wks apart then
  3rd dose at 12-15mos.
• 12-23 months 2 doses, 2 months apart
• 24-59 months HEALTHY 1 dose
  CHRONIC/IMMUNOCOMPROMISED 2 doses, 2 months
  apart
• Previously Vaccinated
• 7-11 months (received 1-2 doses) 2 doses at
  7-11months then 12-15 months, at least 2 months
  apart
• 12-23 months 1 dose, 2 months after last dose
• 24-59 months HEALTHY 1 dose
  CHRONIC/IMMUNOCOMPROMISED 2 doses, 2 mos. apart

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PCV7 (PREVNAR)

• USE (ACIP GUIDELINES)
• All children 2-23 months
• Children gt2-59months with cochlear implants
• Children 24-59months w Sickle Cell dse, Asplenia,
  HIV, immunocompromising/chronic illnesses
• ADVERSE REACTIONS
• gt10
• CNS- fever, irritability, drowsiness,
  restlessness
• Derm erythema
• GI decreased appetite, vomiting, diarrhea
• Local induration, tenderness, nodules
• 1-10
• Derm rash

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PCV7 (PREVNAR)

• CONTRAINDICATIONS
• Hypersensitivity
• Current or Recent Severe/Moderate febrile illness
• PRECAUTIONS
• Caution in latex sensitivity, children with
  coagulation disorders
• DRUG INTERACTIONS
• Immunosuppressants may decrease response to
  active immunizations
• Vaccines may give simultaneously w DTaP, HbOC,
  IPV, Hep B, MMR, Varicella

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PCV7 (PREVNAR)

• MECHANISM OF ACTION
• Promotes active immunization against invasive
  disease caused by S. pneumoniae capsular
  serotypes 4, 6B, 9V, 18 C, 19F, 23F, all of which
  are individually conjugated to CRM19 protein

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2. PPV23 (PNEUMOVAX)

• Purified capsular polysaccharide Ag from 23 types
  of pneumococus (1983)
• 23 serotypes - Account for 88 of bacteremic
  pneumococcal disease
• Cross-react with types causing additional 8 of
  disease
• Not effective in children lt 2 yrs

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PPV23 (PNEUMOVAX)

• IMMUNOGENICITY VACCINE EFFICACY
• gt80 healthy adults develop Abs vs.
  vaccine-related serotypes
• Within 2-3 weeks after vaccination
• Poor Ab response in elderly, w/ chronic illness
  lt2yrs
• Elevated Ab levels persist for at least 5 yrs in
  healthy adults decline more quickly in persons
  w chronic dse
• 60-70 effective in preventing invasive dse
• No protection against pneumococcal PNA

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PPV23 (PNEUMOVAX)

• DOSING
• Previously vaccinated with PCV7
• Sickle cell, Asplenia, HIV, Immunocompromised
• At gt/ 2 yrs at least 2 months after last
  PCV7, revaccination with PPV23 given gt 5 yrs for
  children gt 10 yrs every 3-5 yrs for children lt
  10yrs
• Chronic illness
• At gt 2 yrs gt 2months after last dose of PCV7
  revaccination is not recommended
• Ffing BMT
• 1 dose PPV23 at 12- 24-months ffing BMT

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• ADVERSE REACTIONS
• CV malaise
• CNS GBS, fever, HA, neuropathies
• Derm angioneurotic edema, rash
• GI nausea, vomiting
• Heme hemolytic anemia, thrombocytopenia
• Local injection site rxn
• MS arthritis, mylagia

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• CONTRAINDICATIONS
• Hypersensitivity to pneumococcal vaccine/any
  component
• DRUG INTERACTIONS
• immunosuppressant meds
• Vaccines may be administered w influenza vaccine

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• THE END