Pneumococcal vaccines. Safety & Efficacy. Prof. Rajesh Kumar, MD PGIMER School of Public Health Chandigarh

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1 Pneumococcal vaccines Safety & Efficacy Prof. Rajesh Kumar, MD PGIMER School of Public Health Chandigarh

2 Disclosure Slide X X I DO NOT have any significant or other financial relationships with industry or commercial supporters to disclose. I DO NOT intend to discuss an unlabeled, unapproved, or investigative use of a commercial product or device. Company name(s): I DO have significant or other financial relationships with industry or commercial supporters to disclose as follows: I DO intend to discuss an unlabeled, unapproved, or investigative use or a commercial product or device Please place an X in the boxes as appropriate

3 Pneumococcal vaccines 9: Clinical trials of whole-cell pneumococcal vaccine conducted in South Africa 938: Injection with purified capsular polysaccharides provide clinical protection against type-specific disease 983: 23-valent pneumococcal vaccine licensed 2000: 7-valent pneumococcal conjugate vaccine (PCV) licensed in U.S. 2009: 0-valent PCV vaccine 200: 3-valent PCV introduced 3

4 Pneumococcal Polysaccharide Vaccine (PPSV) Polysaccharide antigen from 23 serotypes Effective in preventing the invasive pneumococcal disease (IPD) Safe vaccine; occasional local side effects Does not reduce nasopharyngeal carriage Does not provide herd immunity Recommended for persons aged 65 years and people in certain high-risk groups aged 2 to 64 year 4

5 Pneumococcal Conjugate Vaccines (PCV) PCV 0 serotypes:, 4, 5, 6B, 7F, 9V, 4, 8C, 9F & 23F PCV 3 serotypes:, 3, 4, 5, 6A, 6B, 7F, 9V, 4,8C, 9A, 9F, 23F 5

6 PCV Efficacy Cochrane Systematic Review of seven studies Invasive pneumococcal disease (IPD): Pooled vaccine efficacy (VE) - For Vaccine Serotypes- 80% (95% CI 58% to 90%, P <0.000) - For All Serotypes- 58% (95%CI 29% to 75%, P = 0.00) Lucero MG, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X- ray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev 2009;(4):CD

7 PCV Efficacy Radiologically defined pneumonia Most studies report radiologically defined pneumonia (standardized WHO definition) - Pooled VE: 27% (95%CI 5% to 36%, P < 0.000) Reduction in pneumonia even in studies that did not follow WHO definition Skinner JM, et al. Pre-clinical evaluation of a 5-valent pneumococcal conjugate vaccine (PCV5-CRM97) in an infant rhesus monkey immunogenicity model. Vaccine 20; 29: Madhi SA, et al. World Health Organization definition of radiologically-confirmed pneumonia may underestimate the true public health value of conjugate pneumococcal vaccines. Vaccine 2007;25(3):

8 PCV Efficacy Clinically defined pneumonia Pooled PE: 6% (2% - 9%, P ) PCV vaccination reduces hospitalization in virus-associated pneumonia; where disease severity is increased by co-infection with pneumococcus Madhi SA, et al. The Vaccine Trialist Group. A role of Streptococcus pneumoniae in virus-associated pneumonia. Nat med 2004;0:

9 PCV Efficacy Otitis media Efficacy of 0-50% against recurrent otitis media or for prevention of tympanostomy tube placement Pneumococcal isolates fell by 39% - 66% among severe otitis media cases or from 'otitis-prone' children 2,3 Fletcher MA, et al. Brief review of the clinical effectiveness of PREVENAR against otitis media. Vaccine. 2007; 25(3): McEllistrem MC, et al. Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2005;40(2): Block SL, et al.. Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J 2004;23(9):

10 PCV Efficacy Nasopharyngeal carriage Most of the available data are on PCV 7 Marked fall in vaccine-type pneumococcal carriage in all age groups (23.7% to 26.8% at baseline to 7.% to 8.5% post-vaccination) Recent studies have reported effectiveness of PCV 2 3 Roca A, et al. Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial. PLoS Med 20;8(0): e Miller E, et al. Effectiveness of the new serotypes in the 3-valent pneumococcal conjugate vaccine. Vaccine. 20;29(49):

11 Safety of PCV PCVs have a well tolerated and acceptable safety profile -3 Main adverse events are injection-site reactions, rash, headache, fatigue, joint pain, fever, decreased appetite Serious rare events include bronchiolitis, pneumonia, gastroenteritis in infants/toddlers Dicko A, et al. Primary vaccination with the 0-valent pneumococcal non-typable Haemophilus Influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial. BMC Public Health 20;: Amdekar YK, et al. Immunogenicity and safety of a 3-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine vaccines in India. Pediatr Infect Dis J. 203 May; 32(5): Lalwani S, et al. Immunogenicity, safety, and reactogenicity of the 0-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study. Hum Vaccin Immunother. 202 May;8(5):62-22.

12 PCV: Efficacy vs Effectiveness Clinically relevant outcomes of public health significance include: mortality, IPD, pneumonia, adverse effects/events Reduces the odds/risk of developing pneumonia, IPD by vaccine serotypes and all-cause mortality (efficacy) Absolute risk reduction is much lower (effectiveness) No major adverse event except a small increase risk of asthma Mathew JL, et al. Effectiveness versus efficacy of conjugated pneumococcal vaccine: a systematic review of randomised, controlled trials with meta-analysis examining absolute risk reduction and relative risk. 2

13 Indian Scenario High case fatality (25-30%) of invasive pneumococcal disease in all age groups Pneumococcus is a predominant pathogen in community acquired acute bacterial meningitis (6.8%) 2 High nasopharyngeal colonization (28%), and High rates of resistance to antibiotics in unvaccinated HIV infected children 3 Thomas K, et al. Invasive pneumococcal disease associated with high case fatality in India.J Clin Epidemiol. 203;66(): Mani R, et al. Bacteriological profile of community acquired acute bacterial meningitis: a ten-year retrospective study in a tertiary neurocare centre in South India. Indian J Med Microbiol. 2007;25(2): Bhattacharya SD, et al. High rates of colonization with drug resistant hemophilus influenzae type B and Streptococccus Pneumoniae in unvaccinated HIV infected children from West Bengal. Indian J Pediatr. 20;78(4):

14 Indian Scenario Efficacy trials on PCV 0, PCV 3 not conducted but studies report immunogencity of these vaccines PCV3 and PCV7: similar safety & tolerability profiles PCV 0, PCV 3 have been licensed and are available in the private sector Pneumococcal vaccination not included in the Indian National Immunization Schedule.Amdekar YK, et al. Immunogenicity and safety of a 3-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine vaccines in India. Pediatr Infect Dis J. 203;32(5):

15 Way Forward Introduction of PCV in National Immunization Schedule Surveillance of pneumococcal serotypes Better diagnostic tools needed to monitor burden of disease 5

16 Thanks 6