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      Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

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          Abstract

          Background

          Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.

          Methods

          We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.

          Results

          Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45,682) per QALY gained. PCV–13 inclusion into the list for single-dose subsidy has an ICER of ¥377,000 (US$3,427) per QALY gained regardless of the PCV–13 diffusion level. These ICERs were found to be cost-effective since they are lower than the suggested criterion by WHO of three times GDP (¥11,000,000 or US$113,636 per QALY gained), which is the benchmark used in judging the cost-effectiveness of an immunisation programmne.

          Conclusions

          The results suggest that switching current PPSV–23 strategy to ≥65 PPSV–23 strategy or including PCV–13 into the list for single-dose subsidy to the elderly in Japan has value for money.

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          Most cited references16

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          Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

          Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
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            Cost-effectiveness of adult vaccination strategies using pneumococcal conjugate vaccine compared with pneumococcal polysaccharide vaccine.

            The cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23) among US adults is unclear. To estimate the cost-effectiveness of PCV13 vaccination strategies in adults. A Markov state-transition model, lifetime time horizon, societal perspective. Simulations were performed in hypothetical cohorts of US 50-year-olds. Vaccination strategies and effectiveness estimates were developed by a Delphi expert panel; indirect (herd immunity) effects resulting from childhood PCV13 vaccination were extrapolated based on observed PCV7 effects. Data sources for model parameters included Centers for Disease Control and Prevention Active Bacterial Core surveillance, National Hospital Discharge Survey and Nationwide Inpatient Sample data, and the National Health Interview Survey. Pneumococcal disease cases prevented and incremental costs per quality-adjusted life-year (QALY) gained. In the base case scenario, administration of PCV13 as a substitute for PPSV23 in current recommendations (ie, vaccination at age 65 years and at younger ages if comorbidities are present) cost $28,900 per QALY gained compared with no vaccination and was more cost-effective than the currently recommended PPSV23 strategy. Routine PCV13 at ages 50 and 65 years cost $45,100 per QALY compared with PCV13 substituted in current recommendations. Adding PPSV23 at age 75 years to PCV13 at ages 50 and 65 years gained 0.00002 QALYs, costing $496,000 per QALY gained. Results were robust in sensitivity analyses and alternative scenarios, except when low PCV13 effectiveness against nonbacteremic pneumococcal pneumonia was assumed or when greater childhood vaccination indirect effects were modeled. In these cases, PPSV23 as currently recommended was favored. Overall, PCV13 vaccination was favored compared with PPSV23, but the analysis was sensitive to assumptions about PCV13 effectiveness against nonbacteremic pneumococcal pneumonia and the magnitude of potential indirect effects from childhood PCV13 on pneumococcal serotype distribution.
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              A 3-year prospective study of a urinary antigen-detection test for Streptococcus pneumoniae in community-acquired pneumonia: utility and clinical impact on the reported etiology.

              To evaluate the efficacy of a rapid immunochromatographic membrane test (ICT) for the detection of Streptococcus pneumoniae urinary antigen for diagnosing S. pneumoniae pneumonia, ICT was performed with urine samples using the Binax NOW Streptococcus pneumoniae kit at the time of admission. The results were compared with those from conventional microbiological studies. Three hundred and forty-nine adult patients with CAP who were admitted to the hospital were studied prospectively between February 2001 and January 2004. The ICT test was positive in 115 (33.0%) of 349 patients enrolled into the study and in 63 (75.9%) of 83 patients with pneumococcal pneumonia confirmed by conventional methods. The test revealed a sensitivity of 75.9% and a specificity of 94.0% with conventional microbiological criteria used as the reference standard. The positive predictive value was 91.3%, and the negative predictive value was 82.6%. The clinical features of 53 patients in whom ICT was positive and no pathogen was identified showed no significant difference from those of 83 patients who had pneumococcal pneumonia identified by conventional methods. The diagnostic yield of pneumococcal pneumonia was increased up to 38.9% using ICT combined with conventional methods. The Binax NOW ICT to detect S. pneumoniae urinary antigen is therefore a rapid and useful method for diagnosing pneumococcal pneumonia. Induction of ICT will prove the predominance of S. pneumoniae in the etiology of CAP.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 October 2015
                2015
                : 10
                : 10
                : e0139140
                Affiliations
                [1 ]Department of Health Care Policy and Health Economics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
                [2 ]Department of Health Care Policy and Health Economics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
                [3 ]Department of Health Care Policy and Health Economics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
                Univ. of Texas Health Science Center at San Antonio, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SLH MK IO. Analyzed the data: SLH. Wrote the paper: SLH.

                Article
                PONE-D-15-26653
                10.1371/journal.pone.0139140
                4596483
                26444287
                3f94a5ca-fa3c-475a-a0c2-2fedae5d736b
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 18 June 2015
                : 8 September 2015
                Page count
                Figures: 4, Tables: 4, Pages: 16
                Funding
                This study was supported by research grant for Research on Emerging and Re-emerging Infectious Diseases, Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare, Japan, and Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, The Ministry of Education, Culture, Sports, Science and Technology.
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