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Background: The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children.Methods: The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods.Results: The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008-June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67-0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5-44.7%), 33.9% (95% CI: 25.2-41.5%) and 43.4% (95% CI: 34.4-51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5-55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2-85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008-June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2-72.3%).Conclusions: PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children. [ABSTRACT FROM AUTHOR]

The most severe form of pneumococcal disease is invasive pneumococcal disease (IPD), including empyema, sepsis and meningitis. Thomsen-Friedenreich antigen (TA; Galβ1-3GalNAc) activation is known to be a predictor of Streptococcus pneumoniae -associated hemolytic uremic syndrome (Sp-HUS). There have been limited data to correlate TA activation and overall disease severity of IPD in children. The study aimed to prove the positive correlation between TA activation and disease severity and to demonstrate the trend of TA level during the disease course. We retrospectively reviewed the medical records from 38 pediatric patients aged from 0 to 18 years with microbiologically-confirmed IPD between 2010 and 2015 at a medical center in Taiwan. All cases underwent TA activation testing by the fluorescence-labeled peanut lectin agglutination method. Medical information including demographic data, laboratory findings, co-morbidities, and outcome was collected and reviewed. We compared the clinical manifestations and associated co-morbidities between TA-positive and TA-negative patients. Among the 38 patients, 25 (66%) showed TA activation. Compared to TA-negative patients, patients with TA activation had a statistically higher rate of prolonged anemia, thrombocytopenia, and acute kidney injury. TA-positive patients also had a longer intensive care unit stay and overall hospitalization days. The TA levels usually peaked 5–10 days after disease onset. Twenty-one pneumococcal isolates were recovered from the patients and serotyping was determined in 11 isolates: 10 serotype 19A and 1 serotype 3. TA determination not only helps to diagnose Sp-HUS but also is a predictor for IPD severity. Among hospitalized patients with severe pneumococcal disease, the peak of TA level usually appeared 5–10 days after disease onset. [ABSTRACT FROM AUTHOR]

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure. [ABSTRACT FROM AUTHOR]

The use of pneumococcal vaccine plays an important role for prevention of invasive pneumococcal disease (IPD). However, introducing the pneumococcal vaccine into the national immunization program (NIP) is complex and costly. The strategy of progressively integrating the pneumococcal conjugate vaccine (PCV) into the NIP in Taiwan provides valuable experience for policy makers. The 7-valent PCV (PCV7) was first available in Taiwan in late 2005. PCV7 was first provided free to children with underlying diseases, those in vulnerable socioeconomic status, and those with inadequate health care resources. The catch-up immunization program with the 13-valent PCV was launched in 2013 and the national pneumococcal immunization program was implemented in 2015. Children aged 2-5 years had the highest incidence of IPD among pediatric population in Taiwan. Although the incidence of IPD caused by PCV7 serotypes has declined, the overall incidence of IPD remained high in the context of PCV7 use in the private sector. A surge of IPD caused by serotype 19A occurred, accounting for 53.6% of IPD cases among children aged ≤ 5 years in 2011-2012. After the implementation of the national pneumococcal immunization program, serogroup 15 has become the leading serogroup for IPD in children. Continued surveillance is necessary to monitor the serotype epidemiology in Taiwan. [ABSTRACT FROM AUTHOR]

Background Pneumococcal infection is a serious cause of mortality and morbidity in the elderly. A nationwide pneumococcal polysaccharide vaccine (PPV) program for elderly adults aged 75 years and older was conducted in Taiwan in 2008. The efficacy of the PPV in this very elderly population was evaluated. Methods The data were analyzed using the Taiwan National Health Insurance Research Database (NHIRD), the cause-of-death registration database and the invasive pneumococcal disease (IPD) notification database of Taiwan's Ministry of Health and Welfare. The efficacy of PPV administration in this very elderly population was evaluated using multivariate logistic regression after propensity score matching (PSM). The rates of IPD, death from IPD, pneumonia hospitalization, death from pneumonia, and all-cause mortality were compared for those who did and did not receive the PPV. Results Among the 1078,955 eligible people, 318,257 (29.5%) received the PPV, and 760,698 (70.5%) were not vaccinated. Using PSM to adjust for confounding factors, including age, gender, influenza vaccination status, associated chronic diseases and health care utilization, those who received the PPV had significantly lower odds ratios (ORs) for IPD (OR = 0.24, 95% CI = 0.123–0.461, p < 0.001), death from IPD (OR = 0.09, 95% CI = 0.011–0.704, p < 0.022, p < 0.001), pneumonia hospitalization (OR = 0.40, 95% CI = 0.395–0.415, p < 0.001), death from pneumonia (OR = 0.07, 95% CI = 0.059–0.082, p < 0.001), and all-cause mortality (OR = 0.07, 95% CI = 0.069–0.072, p < 0.001) compared with those who were not vaccinated. Conclusions PPV vaccination in the previous year was associated with a 60% reduction in pneumonia hospitalization, a 76% reduction in IPD, and a greater than 90% reduction in death from pneumonia, IPD and all causes among people over 75 years old in Taiwan. Data from subsequent years in Taiwan and similar populations elsewhere are needed to evaluate the contribution of underlying variations in the mortality rate and the confounding effects of prior disease severity to these findings. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mandatory national surveillance of IPD in Taiwan began on October 2007. [•] 3659 IPD cases were in 2008–2012, with an incidence of 3.2/100,000 population. [•] Case fatality ratio was 9.2% for all, and 19.0% for adults ≥75 years. [•] PCV7 preventable IPD declined from 59.8% in 2008 to 37.2% in 2012 for all ages. [•] S. pneumoniae serotype 19A became the most prevalent serotype in 2010. [Copyright &y& Elsevier]

Background It is essential to investigate the serotype distribution of pneumococcal diseases in each region and its associated clinical features. This study investigated the annual incidence of invasive pneumococcal disease (IPD) and the distribution of serotypes of isolates causing IPD at a medical center in northern Taiwan during the period 2000 to 2012. Methods Serotypes of all available Streptococcus pneumoniae isolates causing IPD were determined using the latex agglutination test. Results During the study period, the annual incidence (per 10,000 admissions) of IPD decreased significantly from 9.8 in 2000 to 2.1 in 2012 (P < 0.001). The annual incidence of all-cause bacteremia, primary pneumococcal bacteremia, bacteremic pneumonia, peritonitis, and meningitis also decreased significantly during the study period (P < 0.05). In contrast to the decrease in annual incidence of pneumococcal serotypes 14, 23F and 6B, the incidence and the proportion of serotype 19A significantly increased with time (P < 0.001). The coverage rate of 7-valent protein conjugated vaccine (PCV-7) and PCV-10 decreased significantly; however, the coverage rate of PCV-13 and pneumococcal polysaccharide vaccine (PPV-23) remained stable over time. Serotype 14 and 19A isolates were commonly isolated from blood and pleural effusion, respectively. Serotypes 14 and 23F were the two most common serotypes found in adult patients, and serotypes 14 and 19A were the two most common serotypes isolated from children. Conclusions Although the incidence of IPD has decreased, serotype 19A is an emerging problem in Taiwan. The distribution of serotypes of pneumococci varied with clinical symptoms and age. As the changing distribution of pneumococcal serotype with time, the coverage rate of pneumococcal vaccines would be different. [ABSTRACT FROM AUTHOR]

Background/Purpose: Emerging non-7-valent pneumococcal conjugate vaccine (PCV7) serotypes have replaced PCV7 serotypes in childhood invasive pneumococcal disease (IPD). This study was designed to describe the IPD caused by non-PCV7 serotypes under partial PCV7 immunization in Taiwan. Methods: All children <18 years of age diagnosed with IPD at National Cheng Kung University Hospital from 1998 to 2010 were enrolled. Clinical and laboratory information was collected. Pneumococcal isolates were tested for antimicrobial susceptibility and interpreted using Clinical Laboratory Standard Institute guidelines (2008). Serotypes were determined using the capsular swelling method. Results: One hundred and five patients with IPD were identified, including 75 PCV7 and 30 non-PCV7 isolates. Pneumonia (63.3%) was the leading clinical manifestation of non-PCV7 IPDs and 78.9% of pneumonia cases were associated with necrotizing pneumonia or empyema. Children with non-PCV7 IPDs had longer febrile days, required longer intensive care unit stays, and had a higher C-reactive protein level than those with PCV7 IPDs (p < 0.05). Serotype 3 is the most common non-PCV7 serotype (46.7%) and possesses the highest potential for pulmonary complications (p < 0.05, odds ratio: 0.114; 95% confidence interval, 0.013 – 0.973). Conclusion: The changing epidemiology of IPDs following the introduction of PCV7 has been noted. Expanded serotype coverage of the vaccine is warranted. [Copyright &y& Elsevier]

Background: Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan. Methods: A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results. Results: PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations. Conclusions: PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan. [ABSTRACT FROM AUTHOR]

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain 23F -ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.

Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children <5 y of age between January 2008 and December 2008. A prospective survey was administered to the families of patients to obtain detailed personal costs. All costs are presented in US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%-81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection.

Objective: To delineate whether serotype 19A invasive pneumococcal disease (IPD) comprised significantly more necrotizing pneumonia and empyema in children, we compared the clinical characteristics between serotype 19A and non-19A IPD., Methods: Between January 2007 and December 2011, cases of children with IPD who were treated at the National Taiwan University Hospital were reviewed. Patients were assigned to the 19A group or the non-19A group based on the serotype. Their demographic data, clinical course, laboratory results, diagnosis, complications, and sequelae were collected and analyzed., Results: Overall, 27 patients were included in the 19A group and 29 patients in the non-19A group. Compared with non-19A group, serotype 19A tended to cause IPD in patients without major underlying diseases (p = 0.015). Bacteremia without pneumonia or meningitis was found more frequently in the non-19A group (45% vs. 11%, p = 0.01), and pneumonia with or without empyema occurred significantly more frequently in the 19A group (89% vs. 52%, p = 0.006). Patients in the19A group had longer duration of fever (12 vs. 3 days, p = 0.01), and required more intensive care (78% vs. 41%, p = 0.01) and more video-assisted thoracoscopic surgery (74% vs. 28%, p = 0.001)., Conclusion: In comparison with the other serotypes, serotype 19A IPD has significantly more empyema which required more video-assisted thoracoscopic surgery and more intensive care., (Copyright © 2012. Published by Elsevier B.V.)