Pneumococcal Vaccines Update 2011 Prepared for the COI meeting 24 th Dec 2011 Dr Suhas V. Prabhu

Burden of disease - recent updates based on review of literature (national & global); Brief report of any cost-effective analysis published in last 6-12 months; Clinical trials: ongoing/planned/completed; New recommendations from other agencies; Contentious issues, if any.

Burden of Disease –Pneumonet Data* Age group (months) No. of cases No. in group Incidence rate per 1,00,000 population 1 to 638, to 12613, to 24322, to 36422, to 60146, Overall17112, year prospective study Based in 3 Bengaluru hospitals Study of IPD (culture of S. pneumoniae from a normally sterile site) and pneumonia as defined clinically and on X-ray Interim data for 1 year Poster at ESPID- June 2011 * Study Funded by Wyeth, a division of Pfizer Inc. Incidence of IPD in children < 2 years is 15.91(pn) (pyomen) (bact) = 28.28/1,00,000 population

Burden of Disease –Pneumonet Data Age group (months) Clinical Pneumonia No. of cases Incidence rates per 1,00,000 pop. X-ray Pneumonia No. of cases Incidence rates per 1,00,000 pop. 1 to 63934, , to , , to , , to , to , Overall2,3712, , These are total pneumonia cases. Incidence of Pneumococcal pneumonia has to be by extrapolation on possible fraction of S. pneumonae as a cause of pneumonia in this age groups

Burden of disease - recent updates based on review of literature (national & global); Brief report of any cost-effective analysis published in last 6-12 months; Clinical trials: ongoing/planned/completed; New recommendations from other agencies; Contentious issues, if any.

Cost Effectiveness data -Issues Cost effectiveness will depend on whether restricted to “serious diseases” only (IPD) or others like AOM Assumed incidence rates for AOM varied highly in different studies from 20,952 to 118,000 per 1,00,000 children aged 0 – 10 years PCV7 efficacy rates for AOM in 2 early studies were only 6-8% Other studies had rates varying from 12% to 57% depending on vaccine used and whether direct effects alone or additionally herd immunity effects were included Boonacker CV et.al. Pharmacoeconomics 2011 Mar 29(3): doi: /

Cost-effectiveness data – Singapore* PCV-13 prevented 834 cases and 7 deaths due to IPD in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population (herd effect) over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 per QALY. Without herd effect, the ratio was USD $204,535 per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 and for PHiD-10 the ratios were USD $45,100 * Tyo K et. al. Vaccine 29 (2011) 6686– 6694

Cost- effectiveness data – Australia* Potential benefits estimated for PHiD-CV were due primarily to prevention of otitis media and for PCV-13 due to a further reduction in IPD. At equivalent total cost to vaccinate an infant, compared to no PCV the base-case cost per QALY saved were estimated at A$64,900 (for PCV-7; 3 + 0), A$50,200 (for PHiD-CV; 3 + 1) and A$55,300 (for PCV-13; 3 + 0), resp. Assumptions regarding herd protection, serotype protection, otitis media efficacy, and vaccination cost changed the relative cost-effectiveness of alternative PCV programs. The high proportion of current invasive disease caused by serotype 19A (as included in PCV-13) may be a decisive factor in determining vaccine policy in Australia. * Newell AT et. al. Vaccine 29 (2011) 8077– 8085

Cost - Effectiveness data – Mexico* Strategy based on PCV13 prevented deaths, gained QALYs and saved US$1,307/child vaccinated. Strategies based on PCV7 or PCV10 prevented and deaths, gained and QALYs & saved US$ 1,084 and US$ 731/child vaccinated, resp. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. Conclusion: Strategies based on 7, 10 & 13-valent PCVs would be cost-saving interventions, with highest health outcomes and savings of the strategy based on 13-valent vaccine. * Mucino-Ortega E et. al. Value in Health (2011) S65 – 70

Cost-effectiveness – Valencia (Spain) * Universal PCV-13 vaccination would decrease the no. of hospital admitted pneumonia by 4571 cases while avoiding 310 cases of IPD and 82,596 cases of AOM throughout the cohort lifetime. A total of 190 S. pneumoniae related deaths would be averted over the same period. Total medical costs of non-vaccinating the cohort of newborns would reach up to € 403, compared to € 438, for vaccinating the cohort. The incremental cost of vaccinating the children was estimated in € 12,794 per QALY. Conclusion: Universal PCV-13 vaccination would be a cost effective intervention for preventing pneumococcal infections and its associated mortality and morbidity. * Diez-Dominigo J. et. al. Vaccine 29 (2011) 9640–9648

Burden of disease - recent updates based on review of literature (national & global); Brief report of any cost-effective analysis published in last 6-12 months; Clinical trials: ongoing/planned/completed; New recommendations from other agencies; Contentious issues, if any.

Ongoing clinical trials COMPAS study  Being conducted in 24,000 children in 3 Latin American Countries; 4 year follow-up  Aim is to study the efficacy in preventing clinical and radiological pneumonia in study group  PCV10 (with NTHi D protein) in study arm with control (Hep. B and Hep. A)  Interim data – vaccine efficacy rate of 22% (clinical pneumonia i.e. features of LRTI with CRP > 40 mg/L) and 25.7% (Consolidation on X-ray Chest)  Likely to be officially published in March/June 2012

Other Efficacy data PHiDCV (PCV10) introduced in Brazil from children randomly selected from Central Brazil from Dec 2010 to Mar 2011 Effectiveness of pneumococcal NP carriage for incomplete and completely vaccinated children were 26% (95% CI: 0%-50%) and 36%(95% CI: 12%- 53%), respectively. For CAP, the effectiveness for complete vaccinated children was 40% (95% CI: 1.4%-63%). Andrade AL et al. Presented at WSPID, Melbourne, Nov 2011

PCV7 and PCV13 prevents meningitis Municipality of Campos (Rio de Janeiro) introduced free PCV7 in children under one year old from 05/29/2009, until 10/24/2010, when it was replaced by PCV13. Primary doses at 3, 5, 7 months, with booster dose at 13 months age. After 19 months of vaccination, at least 6,440 children received 4 doses of vaccine, with 92% of coverage vaccination status (7.000 births/year). There was no suspect or confirmed pneumococcal meningitis case in 2010, when compared with 2009, when there were notified 5 cases, and 1 death. Kury CM et al. Presented at WSPID Melbourne Nov 2011

Acute Bacterial Core surveillance data (US)* Rates of IPD with all serotypes per 1,00,000 pop. In children < 2 years of age (Total cases) Effect of switch to PCV13 in Feb 2010 All serotypes Vaccine serotypes Quarter/YearBaseline Baseline Jan-Mar Apr-Jun Jul-Sept Oct * * * P < Conclusion: These preliminary findings are consistent with early effects of PCV13 on IPD among young children *Presented at ICAAC of ASM at Chicago Sept. 2011

Burden of disease - recent updates based on review of literature (national & global); Brief report of any cost-effective analysis published in last 6-12 months; Clinical trials: ongoing/planned/completed; New recommendations from other agencies; Contentious issues, if any.

New recommendations for PCV 10 Iceland – PCV10 April EMA(CMPH) – PCV10 June (extension of use for 2 to 5 year age group) Brazil, Chile, Mexico, Colombia Finland, Sweden, Netherlands Albania, Bulgaria, Austria, Cyprus Kenya 1. EPI-ICE 7:2 Apr-Jun NELM News Service June 2011

New recommendations – PCV10 vs PCV13 Switch from PCV 10 to PCV 13  Hong Kong Nov  AustraliaAug  CanadaSep Simultaneous use of PCV10 and PCV 13  Korea Apr No comment of superiority or otherwise of either vaccine No special recommendation for use of either vaccine in any specific group  New ZealandMay Use of PCV10 routinely and PCV13 for “high-risk” group 1. Press Release: Health Dept. HK. Nov 29, Dept. Memo dated 30th Aug, CCDR: Nov Korean J Pediatr 2011;54(4): IAC – Univ. of Auckland

New recommendations – schedules of vaccination schedule  Colombia (Bogotá), Finland, Mexico, Sweden (3 provinces)  U.K., France, Belgium schedule  Australia (Northern Territories), Austria (high-risk groups), Albania, Brazil, Bulgaria, Cyprus (high-risk groups), Hong Kong, Taiwan (Taipei), The Netherlands, Germany schedule  Kenya N.B. PCV13 now recommended for adults aged 50 years and over

Are 2 primary doses adequate? Review of 8 RCTs on PCV7 in 10 countries Immunological data: 3p schedules result in slightly higher antibody levels than 2p schedules both before and after a booster dose, particularly for serotypes 6B and 23F. There is an absence of clinical outcome data Limited data re: nasopharyngeal carriage from direct comparisons of any 2p to any 3p schedule. P. Scott et al. Vaccine 29 (2011) 9711–9721

Burden of disease - recent updates based on review of literature (national & global); Brief report of any cost-effective analysis published in last 6-12 months; Clinical trials: ongoing/planned/completed; New recommendations from other agencies; Contentious issues, if any.

Contentious Issues – Additional categories in high risk group Prematurity and VLBW babies Up to 9 fold higher incidence of IPD in VLBW babies compared to full size babies* Is included as high risk category by many advisory bodies incl. ACIP (USA), New Zealand IAP COI recommendations 2010 do not include this category as “high-risk” Need to correct this lacuna in next publication * Shinefield H et al. Pediatr Infect Dis J.2002;21:182-6

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