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Pneumococcal Vaccine in Children

Pneumococcal Vaccine in Children. Pneumococcal Vaccine in Children Dr. Kwan Yat-wah Department of Paediatrics and Adolescent Medicine Princess Margaret Hospital. Streptococcus pneumoniae ( Pneumococcus). Gram Positive, -hemolytic encapsulated diplococcus

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Pneumococcal Vaccine in Children

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  1. Pneumococcal Vaccine in Children Pneumococcal Vaccine in Children Dr. Kwan Yat-wah Department of Paediatrics and Adolescent Medicine Princess Margaret Hospital

  2. Streptococcus pneumoniae(Pneumococcus) • Gram Positive, -hemolytic encapsulated diplococcus • Polysaccharide capsule define the serotype – 91 distinct capsular types • Welcome 6C # • Prevalence spectrum varies with age, geographical region #Park IH. Discovery of a New Capsular Serotype (6C) within Serogroup 6 of Streptococcus Pneumoniae. Journal of Clinical Microbiology 2007; 45:1225-1233

  3. The Pneumococcus • Major cause of respiratory disease and bacterial meningitis worldwide

  4. Invasive Pneumococcal Disease (IPD) • Case Definition: • Isolation of Streptococcus Pneumoniae from a normally sterile site (not including middle ear) or • Demonstration of Streptococcus Pneumoniaeantigen in Cerebrospinal Fluid

  5. Invasive pneumococcal disease (IPD) • Pneumonia with bloodstream infection, septicemia, meningitis • Localized respiratory disease • Middle ear infections, sinusitis, bronchitis, pneumonia

  6. Capsule Polysaccharide • Define the virulence • The main target of vaccine intervention

  7. Epidemiology

  8. Epidemiology • Very common in the very young and very old • Reservoir: Human, colonization in the upper respiratory tract of healthy people • Transmission: Respiratory droplets, direct oral contacts, indirectly through articles freshly soiled with respiratory discharges • Incubation Period: 1-3 days

  9. Invasive Pneumococcal Disease Incidence by Age Group England and Wales 2000 (pre-PCV7) Germany: 8.9 per 100,000 children; Switzerland: 7.6 per 100,000 children England and Wales: 14.5 per 100,000 children Health Protection Agency Communicable Disease Surveillance Centre. CDR Weekly 2003; 12(21)

  10. Nasopharyngeal carriage • Gambia: 76.1 – 85.1 • Pakistan: 51.9 – 64.4% • Philippines: 51 – 62% • South Africa: 29.4% • Southern Israel: 35% - 93% • Uruguay: 15.2 – 42.1% • Zambia: 71.9%

  11. 60% 60 50 35% 40 29% Carriage rate (%) 25% 30 20 6% 10 0 Preschool Grammar school Jr. HighSchool Households with children Householdswithout children Nasopharyngeal carriage of Pneumococcus 1 Presentation by Mark A. Fletcher, M.D., on Epidemiology of Streptococcus pneumoniae: “Pneumococcus”

  12. Burden of Pneumococcal Disease

  13. Pneumonia • Largest infectious Disease Causes of Child Death Worldwide* • Can be bacterial / viral, but the 1st cause if Streptococcus Pneumoniae • Responsible for >1 million child deaths annually • In developed countries, high morbidity (empyema, ..) and adult carries most of the burden of the disease *UNICEF 2006: Pneumonia, the forgotten killer of children WHO 2003; Levine 2006

  14. Burden of Pneumococcal Disease • Overall burden is difficult to estimate • Problems inherent in establishing bacterial etiology in people with pneumonia, bacteraemia, meningitis or otitis media

  15. Prevalence of IPD varies with • Geographical region • Risk Factors: • Age • Underlying diseases • Ethnic Groups

  16. Incidence of IPD in children < 2yrs old 206.8 150 37.1-48.1 96.4 18.9 UK Australia HONG KONG Argentina South California Robinson KA JAMA 2001; Davidson M JID 1994; O’Dempsey TJ PIDJ 1996: Levine MM PIDJ 1998; Cortese MM Arch Intern Med 1992; Torzillo PF Med J Austr 1995; Eskola J JAMA 1992; Berkley NEJM 2005

  17. Young Children – High Risk • Risk factors for IPD are: • Children < 2 years of age • Underlying disease • Children who attend daycare in previous 3 months • Risk factors for penicillin-resistant IPD • Children exposed to > 1 course of antibiotics • Children with history of > 1 recent ear infection • in previous 3 months • OS Levine, M Farley, et. al. Risk factors for Invasive Pneumococcal Diseases in Children: A Population-Based Case-Control Study in North America. Pediatrics 103; 3: 1999

  18. A Finnish study (children < 2 years) who • attended daycare provided outside the home had a 36-fold  in risk of IPD • attended family daycare had a 4.4-fold 

  19. Risk for IPD

  20. Invasive Pneumococcal Disease Incidence by Age Group England and Wales 2000 (pre-PCV7) Germany: 8.9 per 100,000 children; Switzerland: 7.6 per 100,000 children England and Wales: 14.5 per 100,000 children Health Protection Agency Communicable Disease Surveillance Centre. CDR Weekly 2003; 12(21)

  21. Situation in Hong Kong

  22. Annual incidence of culture-confirmed IPD, Hong Kong Island, by age, 1995-2004. 18.8 Rate for children <5 y: 15.6 (12.8-18.6) Invasive pneumococcal disease (IPD) based on all positive cultures (blood, CSF, body fluid) in two major hospitals (Queen Mary Hospital and PYH) representing 90% of all cases on Hong Kong island, 1995-2004. Population figures from sub-census in 1996 and 2001 used in calculation. P L Ho, et al, The Paediatric Infection Disease Journal, Vol 25 (5) 454-455 May 2006

  23. Disease burden in Hong Kong • Incidence of Invasive Pneumococcal Disease per 100 000 children < 5 yr* • Meningitis: 1 case • Bacteraemia: 20 cases • Pneumonia: 100 cases • The most common serotype: • 14, 6B, 19F, 23F# (Licensed PCV7 contains: 4, 6B, 9V, 14, 18C, 19F and 23F) *Hong Kong Journal of Pediatric (New Series) 2001: 6: 127 – 132 #Dr. PL Ho et al. Vaccine 22 (2004), 3334-3339

  24. Penicillin resistance in Hong Kong 13 Jacobes et al, ICAAC 1999 poster #1044

  25. Vaccination against Pneumococcus Capsular antibodies directed vs specific serotypes

  26. Vaccination • Pneumococcal Polysaccharide vaccine (Pneumovax) • Directed against 23 capsular serotypes • Overall protective efficacy of 60-70%

  27. Recommendation for Polysaccharide Pneumococcal Vaccine • Healthy elderly people (> 65 years of age), particularly those living in institutions • Patients with chronic cardiopulmonary disease, DM, alcoholism, chronic liver disease, CSF leak • Particular immunodeficiencies • Children with high risk- sickle cell anaemia or splenectomized

  28. Problems with polysaccharide vaccine in children • Not effective in children less than 2 years • No effect on nasal carriage • No herd effect • Absence of immunologic memory • Antibody level to several serotypes decline to pre-vaccination values within 3-7 years corresponding to a decline of clinical protection

  29. Conjugate Vaccine • A new generation of pneumococcal vaccines • Coating removal of the capsular polysaccharide • 7 (9, 11 or 13, …) types of saccharide is separately activated and conjugated to protein carrier • Conjugates are mixed to formulate vaccine

  30. Conjugate Vaccine • induce a T-cell dependent immune response. • These vaccines are protective even in children under two years of age, and may reduce pneumococcal transmission through a herd effect

  31. Prevenar (PCV7) • Serotypes contained in the vaccine • (4, 6B, 9V, 14, 18C, 19F, 23F) • The serotypes included responsible for • 85% of pneumococcal diseases and • 70% of IPD in the States • 65-80% in Western Industrialized countries (WHO position paper) • These saccharides are coupled to a nontoxic mutant of diphtheria toxin and the protein CRM197.

  32. Coverage by PCV7 in Hong Kong • Serotype: 14, 6B, 19F, 23F# • (Licensed PCV7 contains: • 4, 6B, 9V, 14, 18C, 19F and 23F) Dr. PL Ho et al. Vaccine 22 (2004), 3334-3339 * resistance to penicillin, erythromycin and cefotaxime

  33. Immunogenicity • 212 healthy 2-month-old infants from four communities across US • After 3 doses of vaccine, increasing trend of the geometric mean antibody concentrations (GMCs) were demonstrated • Administration of the 4th dose demonstrating a brisk anamnestic response Rennels MB, Edwards KM, Keyserling HL, et al. Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 in United States infants. Pediatrics. 1998;101:604-611

  34. The Impact of Pneumococcal Conjugate Vaccine on Pneumococcal Disease

  35. Direct Effect Among Children

  36. Kaiser Permanente Vaccine Study: • North Carolina Oct 1995 to Apr 1999 • 37,868 healthy infants (randomized double blinded) • PCV7 (study group) or the meningococcus type C conjugate vaccine (control group) • PCV7 contains serotypes responsible for 85% of pneumococcal diseasein infants / children in studied population. • The vaccines were administered at 2, 4, 6 and 12 to 15 months of age, along with the standard immunization schedule • Black S, Shinefield H, Fireman B, et al.  Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children.  Pediatric Infectious Disease Journal 2000; 19:187-195

  37. Efficacious in Preventing IPD • 97.4% efficacy fully immunized children • 93.9% efficacy in intention to treat analysis • 89.1% effective in reducing overall IPD regardless of serotype • No increased in non-vaccine serotype IPD • Black S, Shinefield H, Fireman B, et al.  Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children.  Pediatric Infectious Disease Journal 2000; 19:187-195 PCV only cover 85% IPD serotypes ?? Cross Protection

  38. Kaiser Permanente Vaccine Study – Postlicensure surveillance study • Northern California Kaiser Permanente population • April 1996 to March 2003 • Incidence of IPD dramatically reduced in children < 2 yrs old • Black S, Shinefield H, Baxter R, et al. Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser Permanente. Pediatr Infect Dis J. 2004;23:485-489

  39. IPD 51.5 – 98.2 IPD 81.7 – 113.8 Steven Black et al; The Pediatric Infectious Disease Journal, Vol. 23, Number 6, June 2004; 485-489

  40. Pneumococcal Conjugate Vaccine Effectiveness Study • USA Centers for Disease Control and Prevention Active Bacterial Core surveillance • Matched Case-control study • Whitney CG. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study. • The Lancet 2006; 368:1495-151502

  41. Effective by serotype and Presence of Underlying Medical Conditions N=782 cases and N=2512 Control * Case / Control sets with chronic or Immunocompromised medical condition present • Whitney CG. The Lancet 2006; 368:1495-151502

  42. Cumulative Weekly Number of Reports of Invasive Pneumococcal Disease Due To One of the Seven Serotypes Present in Prevenar™ for Children Aged 0-2 Years in England and Wales by Epidemiological Year: July-June (2003 to Date) The 7-valent conjugate vaccine was introduced into the childhood immunization schedule on the 4th September 2006, which corresponds with week 36 above http://www.hpa.org.uk/infections/topics_az/pneumococcal/default.htm

  43. Cumulative Weekly Number of Reports of Invasive Pneumococcal Disease Due To One of the Serotypes Not Present in Prevenar™ for Children Aged 0-2 Years in England and Wales by Epidemiological Year: July - June (2003 to Date) The 7-valent conjugate vaccine was introduced into the childhood immunization schedule on the 4th September 2006, which corresponds with week 36 above http://www.hpa.org.uk/infections/topics_az/pneumococcal/default.htm

  44. Efficacy Studies on Otitis Media

  45. Kaiser Permanente Vaccine Study: • Reduce OM visits 8.9%, OM episodes 7.0%, frequent OM 9.3%. Tubes placement 20.1% (all p<0.04), • If tympanocentesis done, serotype specific efficacy 66.7% • Black S, Shinefield H, Fireman B, et al.  Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children.  Pediatric Infectious Disease Journal 2000; 19:187-195

  46. Efficacy Against Otitis Media in Finland Not sig. • 1662 infants • Overall reduction of acute OM 6% (CI –4 to 16%) • Reduction in cultured confirmed pneumo OM 34% • Reduction in OM from vaccine serotypes: 57% • 6B, 14, 23F, (good), 19F (poor) • 6A (X-react good), 19A (poor) • Increase in non-vaccine serotype pneumo OM 33% • Eskola, etal. Efficacy of a Pneumococcal Conjugate Vaccine against Otitis Media. NEJM 2001; 344:403-409 25% 84%

  47. Effectiveness on Serotypes

  48. Vaccine effectiveness according to serotype • Effective against all 7 vaccine serotypes individually, the poorest response is to 19F • Effective against vaccine-related 6A; • Not effective against vaccine-related serotype 19A

  49. Nasopharyngeal Carriage

  50. Studies have shown that pneumococcal immunization decrease carriage of vaccine serotypes • Studies also showed a decrease in carriage of PNSP types

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