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AbstractAimsV114, a 15-valent pneumococcal conjugate vaccine (PCV15) currently approved in adults in the US, contains the 13 S. pneumoniaeserotypes in PCV13 and two additional serotypes, 22 F and 33 F, which are important contributors to residual PD. This study quantified the health and economic burden of pediatric invasive pneumococcal disease (IPD) associated with V114 serotypes in eight countries in Europe.Materials and methodsA Markov model estimated V114-type IPD cases and costs in hypothetical unvaccinated birth cohorts from Denmark, France, Germany, Italy, Norway, Spain, Switzerland, and the UK over 20 years. Inputs were obtained from published literature. IPD cases and costs were calculated for three time periods using time-specific epidemiological data: (a) pre-PCV7; (b) pre-PCV13; and (c) post-PCV13. Costs were estimated from a societal perspective (2018 Euros) and discounted at 3%.ResultsThe model estimated that 4,649 IPD cases in the pre-PCV7 period, 3,248 cases in the pre-PCV13 period, and 958 cases in the post-PCV13 period were attributable to V114 serotypes. Total discounted costs associated with V114 serotypes were €109.1 million (pre-PCV7 period), €65.7 million (pre-PCV13 period), and €18.7 million (post-PCV13 period).LimitationsPost-meningitis sequelae, acute otitis media, and non-bacteremic pneumonia were not considered. Direct non-medical costs were not included. Conclusions on effectiveness of V114 or added value over existing infant vaccination programs cannot be drawn.ConclusionsIPD cases and costs were estimated in hypothetical birth cohorts in eight European countries followed for 20 years during three time periods. Serotypes included in V114 were associated with significant morbidity and costs in pre-PCV7, pre-PCV13, and post-PCV13 periods. Future pediatric pneumococcal vaccines should maintain protection against serotypes in licensed vaccines while extending coverage to additional serotypes to ensure reductions in IPD burden are maintained.

AbstractAimsV114 is an investigational 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 Streptococcus pneumoniaeserotypes in 13-valent PCV (PCV13) plus two additional serotypes. This study quantified the health and economic burden of invasive pneumococcal disease (IPD) and acute otitis media (AOM) caused by V114 types among children in the United States.Materials and methodsA Markov model estimated the number of V114-type IPD and AOM cases and costs in a hypothetical, unvaccinated US birth cohort over 20 years. Three time periods were analyzed using time-specific epidemiological data to determine the number of IPD and AOM cases associated with all 15 serotypes in V114. The time periods were: (1) pre-PCV7 (1999); (2) pre-PCV13 (2009); (3) post-PCV13 (2017). Costs were estimated from a societal perspective (2018 US dollars) and discounted at 3%.ResultsThe model estimated 18,983 IPD cases and 5.4 million AOM cases associated with V114 serotypes pre-PCV7, 4,697 IPD cases and 3.0 million AOM cases pre-PCV13, and 948 IPD cases and 0.2 million AOM cases post-PCV13. Total discounted costs associated with V114 serotypes were $1.7 billion pre-PCV7, $730 million pre-PCV13, and $75 million US dollars post-PCV13.LimitationsPost-meningitis sequelae, cases of non-bacteremic pneumonia, and direct non-medical costs were not included.ConclusionsIPD and AOM cases and costs were estimated in a hypothetical US birth cohort followed for 20 years at three time periods. In all three periods, the serotypes targeted by V114 contributed to significant morbidity and costs. New pediatric pneumococcal vaccines must continue to retain serotypes in licensed vaccines to maintain disease reduction while extending coverage to non-vaccine serotypes.

AbstractObjective:In Japan, the National Immunization Program (NIP) includes PPV23 as the primary vaccination for adults and catch-up cohorts. The Japanese Association for Infectious Diseases recommends revaccination for older adults who received primary vaccination ≥5 years earlier. The cost-effectiveness of adding revaccination and/or continuing catch-up vaccination in the NIP was evaluated from the public payer perspective in Japan.Methods:The Markov model included five health states: no pneumococcal disease, invasive pneumococcal diseases (IPD), non-bacteremic pneumococcal pneumonia (NBPP), post-meningitis sequelae, and death. Cohorts of adults aged 65–95 were followed until age 100 or death: 2014 cohort (aged 65–95, vaccinated: 2014); 2019 cohort (aged 65: 2019); and 2019 catch-up cohort (aged 70–100: 2019, unvaccinated: 2014). Strategies included: (1) vaccinate 2014 and 2019 cohorts; (2) vaccinate 2014 and 2019 cohorts and revaccinate both; (3) strategy 1 and vaccinate 2019 catch-up cohort; (4) strategy 2 and vaccinate 2019 catch-up cohort; and (5) strategy 4 and revaccinate 2019 catch-up cohort. Parameters were retrieved from global and Japanese sources, costs and QALYs discounted at 2%, and incremental cost-effectiveness ratios (ICERs) estimated.Results:Strategy 1 had the highest number of IPD and NBPP cases, and strategy 5 the lowest. Strategies 3–5 dominated strategy 1 and strategy 2 was cost-effective compared to strategy 1 (ICER: ¥1,622,153 per QALY gained). At a willingness-to-pay threshold of ¥5 million per QALY gained, strategy 2 was cost-effective and strategies 3–5 were cost-saving compared to strategy 1.Conclusions:Strategies including revaccination, catch-up, or both were cost-effective or cost-saving in comparison to no revaccination and no catch-up. Results can inform future vaccine policies and programs in Japan.

ABSTRACTVaccinations against Streptococcus pneumoniaeare included in infant immunization programs globally. However, a substantial burden due to pneumococcal disease (PD) remains. This study aimed to estimate the cost of emergency department (ED) visits and hospitalizations associated with invasive pneumococcal disease, all-cause pneumonia, and acute otitis media in children <15 years of age in the Liguria region of Italy between 2012 and 2018. The retrospective cohort study used data from the Liguria Region Administrative Health Databases and the Ligurian Chronic Condition Data Warehouse, which contain information on hospital stays, outpatient visits, laboratory/imaging techniques, surgical procedures, and pharmaceutical prescriptions. Patients with one or more ED or inpatient claim for PD (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes) were included. Cost of ED visits and hospitalizations were estimated from the diagnosis-related group system and procedures performed in the ED. In Ligurian children <15 years of age during 2012–2018, the median annual number of hospitalizations plus ED visits due to PD was 4,009, and the median estimated annual cost was €3.6 million. All-cause pneumonia accounted for the majority of hospitalization costs during the study period. Number and costs of ED visits and hospitalizations increased from 2012 to 2018. Despite widespread infant immunization in Liguria, economic costs due to PD-associated ED visits and hospitalizations remained high in children 0–14 years of age.

IMPORTANCE: Mortality is an important measure of the severity of a pandemic. This study aimed to understand how mortality by age of hospitalized patients who were tested for SARS-CoV-2 has changed over time. OBJECTIVE: To evaluate trends in in-hospital mortality among patients who tested positive for SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients who were hospitalized for at least 1 day at 1 of 209 US acute care hospitals of variable size, in urban and rural areas, between March 1 and November 21, 2020. Eligible patients had a SARS-CoV-2 polymerase chain reaction (PCR) or antigen test within 7 days of admission or during hospitalization, and a record of discharge or in-hospital death. EXPOSURE: SARS-CoV-2 positivity. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection was defined as a positive SARS-CoV-2 PCR or antigen test within 7 days before admission or during hospitalization. Mortality was extracted from electronically available data. RESULTS: Among 503?409 admitted patients, 42?604 (8.5%) had SARS-CoV-2–positive tests. Of those with SARS-CoV-2–positive tests, 21?592 (50.7%) were male patients. Hospital admissions among patients with SARS-CoV-2–positive tests were highest in the group aged 65 years or older (19?929 [46.8%]), followed by those aged 50 to 64 years (11?602 [27.2%]) and 18 to 49 years (10?619 [24.9%]). Hospital admissions among patients 18 to 49 years of age increased from 1099 of 5319 (20.7%) in April to 1266 of 4184 (30.3%) in June and 2156 of 7280 (29.6%) in July, briefly exceeding those in the group 50 to 64 years of age (June: 1194 of 4184 [28.5%]; 2039 of 7280 [28.0%]). Patients with SARS-CoV-2–positive tests had higher in-hospital mortality than patients with SARS-CoV-2–negative tests (4705 [11.0%] vs 11?707 of 460?805 [2.5%]; P?&lt;?.001). In-hospital mortality rates increased with increasing age for both patients with SARS-CoV-2–negative tests and SARS-CoV-2–positive tests. In patients with SARS-CoV-2–negative tests, mortality increased from 45 of 11?255 (0.4%) in those younger than 18 years to 4812 of 107?394 (4.5%) in those older than 75 years. In patients with SARS-CoV-2–positive tests, mortality increased from 1 of 454 (0.2%) of those younger than 18 years to 2149 of 10?287 (20.9%) in those older than 75 years. In-hospital mortality rates among patients with SARS-CoV-2–negative tests were similar for male and female patients (6273 of 209?086 [3.0%] vs 5538 of 251?719 [2.2%]) but higher mortality was observed among male patients with SARS-CoV-2–positive tests (2700 of 21?592 [12.5%]) compared with female patients with SARS-CoV-2–positive tests (2016 of 21?012 [9.60%]). Overall, in-hospital mortality increased from March to April (63 of 597 [10.6%] to 1047 of 5319 [19.7%]), then decreased significantly to November (499 of 5350 [9.3%]; P?=?.04), with significant decreases in the oldest age groups (50-64 years: 197 of 1542 [12.8%] to 73 of 1341 [5.4%]; P?=?.02; 65-75 years: 269 of 1182 [22.8%] to 137 of 1332 [10.3%]; P?=?.006; >75 years: 535 of 1479 [36.2%] to 262 of 1505 [17.4%]; P?=?.03). CONCLUSIONS AND RELEVANCE: This nationally representative study supported the findings of smaller, regional studies and found that in-hospital mortality declined across all age groups during the period evaluated. Reductions were unlikely because of a higher proportion of younger patients with lower in-hospital mortality in the later period.