PNEUMOCOCCAL VACCINE

1. PNEUMOCOCCAL VACCINE Charisse De Los Reyes, M.D.

2. 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

3. 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

4. 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

5. 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

6. SPUTUM FR PNEUMOCOCCAL PNA

7. 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

8. 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 < 6yrs account for 80% infections; account for only ~50% isolates

9. 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

10. ADHERENCE

11. 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

12. 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

13. 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

14. 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

15. 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

16. COMPLICATIONS OF PNEUMOCOCCAL PNA

17. 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

18. PNEUMOCOCCAL DISEASE IN CHILDREN BACTEREMIA(w/o a known infxn site) Most common CP in <2 yrs 70% of invasive dse in this age MENINGITIS leading cause of bacterial meningitis (W decline of invasive Hib) in <5yrs PNEUMONIA 12-16% of invasive pneumococcal dse <2yrs OTITIS MEDIA 28-55% of middle ear aspirates

19. BURDEN OF PNEUMOCOCCAL DISEASE IN CHILDREN**Prior to routine use of pneumococcal conjugate vaccine

20. 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

21. 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

22. RESISTANCE

23. MEDICAL MANAGEMENT

24. PNEUMOCOCCAL DISEASE EPIDEMIOILOGY

25. TYPES OF PNEUMOCOCCAL VACCINE Pneumococcal conjugate vaccine (7-valent) Prevnar Dosing: 0.5mL IM Pneumococcal polysaccharide vaccine (23-valent) Pneumovax Dosing:0.5mL IM/SC

26. USE OF PNEUMOCOCCAL VACCINE

27. 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 <6 yrs

28. PPV7 (PREVNAR) IMMUNOGENICITY & VACCINE EFFICACY After 4 doses, >90% 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

29. 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

30. PCV7 (PREVNAR) USE (ACIP GUIDELINES) All children 2-23 months Children >2-59months with cochlear implants Children 24-59months w Sickle Cell dse, Asplenia, HIV, immunocompromising/chronic illnesses ADVERSE REACTIONS >10% CNS- fever, irritability, drowsiness, restlessness Derm � erythema GI � decreased appetite, vomiting, diarrhea Local � induration, tenderness, nodules 1-10% Derm: rash

31. 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

32. 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

33. 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 < 2 yrs

34. PPV23 (PNEUMOVAX) IMMUNOGENICITY & VACCINE EFFICACY >80% healthy adults develop Abs vs. vaccine-related serotypes Within 2-3 weeks after vaccination Poor Ab response in elderly, w/ chronic illness & <2yrs 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

35. PPV23 (PNEUMOVAX) DOSING Previously vaccinated with PCV7: Sickle cell, Asplenia, HIV, Immunocompromised At >/= 2 yrs & at least 2 months after last PCV7, revaccination with PPV23 given > 5 yrs for children > 10 yrs & every 3-5 yrs for children < 10yrs Chronic illness At > 2 yrs & > 2months after last dose of PCV7; revaccination is not recommended Ff�ing BMT 1 dose PPV23 at 12- & 24-months ffing BMT

36. 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

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

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