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Background: Influenza is a contagious respiratory illness responsible for seasonal epidemics and with potential to cause pandemics. The decline in influenza-related studies published since 2018 resulted in data gaps, particularly in emerging markets. Methods: This systematic review searched for studies in six databases and gray literature sources to define the clinical burden of influenza and influenza-like illness (ILIs) and their associated sequelae among humans across emerging markets. Eligible studies were published in English, Spanish, or Chinese between January 2018 and September 2023 and conducted in Asia, the Middle East, Africa, and Latin America. Results: In total, 256 articles were included, mostly on lab-confirmed influenza infections (n = 218). Incidences of lab-confirmed influenza cases in Asia (range 540–1279 cases/100,000 persons) and Sub-Saharan Africa (range 34,100–47,800 cases/100,000 persons) were higher compared to Latin America (range 0.7–112 cases/100,000 persons) and the Middle East and North Africa (range 0.1–10 cases/100,000 persons). Proportions of lab-confirmed influenza cases and influenza-associated outcomes (i.e., hospitalization, ICU admission and death) varied widely across regions. Temporal variation in influenza trend was observed before and during the COVID-19 pandemic. Conclusions: In conclusion, influenza causes significant disease burden in emerging markets. Robust large real-world studies using a similar methodology are needed to have more accurate estimates and compare studies within age groups and regions. Continuous monitoring of influenza epidemiology is important to inform vaccine programs in emerging markets with heavy influenza disease burden. [ABSTRACT FROM AUTHOR]

A correction notice was issued for a study on severe COVID-19 outcomes in five Latin American countries in the post-vaccination era, addressing an error in reported hospitalized cases in Brazil. The study analyzed clinical profiles, hospitalization rates, mortality rates, and vaccination status of confirmed COVID-19 cases, highlighting differences in outcomes between males and age groups, as well as the impact of comorbidities and COVID-19 variants on hospitalization rates. Detailed data on COVID-19 cases, mortality rates, ICU admissions, comorbidities, and vaccination status by age group is provided for Brazil, Mexico, Colombia, Argentina, and Chile, offering insights into the pandemic's impact in different regions. The authors have made corrections to ensure the scientific accuracy of their conclusions. [Extracted from the article]

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. We analyzed the sociodemographic characteristics, comorbidities, clinical outcomes, and vaccination status of laboratory-confirmed COVID-19 cases from January 2021 to December 2022. We calculated the yearly and quarterly hospitalization rates per 1000 confirmed COVID-19 cases and ICU admissions, use of mechanical ventilators, and mortality rates per 1000 hospitalized cases, with their corresponding 95% confidence interval (CI) of 38,852,831 confirmed COVID-19 cases. Rates of hospitalization, ICU admission, ventilatory support, and death were higher among males than among females (38.2 vs. 32.4, 148.4 vs. 117.7, 282.9 vs. 236.2, and 346.9 vs. 320.1 per 1000, respectively); higher in 2021 than in 2022 (50.7 vs. 19.9, 207.8 vs. 58.2, 441.5 vs. 114.9, and 352.5 vs. 285.2 per 1000, respectively); and in the >50 age group (range: 5.7–18.6, 20.1–71.5, 12.2–67.9, and 353.1–577.4, per 1000) than the <50 age group (range: 2.2–9.3, 5.4–33.2, 41.4–135.8, and 22–243.5 per 1000). Hypertension and diabetes mellitus were the most common comorbidities in Mexico and Colombia. Prevention and treatment strategies for these case profiles could bring benefits from a public health perspective. [ABSTRACT FROM AUTHOR]

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children's Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants. [ABSTRACT FROM AUTHOR]

Background Antivirals are effective in reducing hospitalisation and death in mild-to-moderate coronavirus 2019 (COVID-19) patients. We estimated the antiviral uptake of nirmatrelvir/ritonavir and molnupiravir in adult patients with a syndrome coronavirus 2 (SARS-CoV-2) infection during the Emergency Use Authorization (EUA) period in Taiwan. Methods A retrospective cohort study was conducted in Taiwan between January 2022 and December 2022. Patients aged ≥18 years with a SARS-CoV-2 infection were included from the Taipei Medical University Clinical Research Database (TMUCRD) and stratified in three risk groups according to World Health Organization criteria. Results In total, 96 398 COVID-19 patients (mean age 46.7 ± 17.7 years, 45.8% male) were included. Of these patients 69.8% were classified as low risk, 29.8% as moderate risk, and 0.4% as high risk for progression to severe COVID-19. Nirmatrelvir/ritonavir was prescribed in 5.1% of the COVID-19 patients (low risk = 1.0%, moderate risk = 14.3%, high risk = 17.6%). Molnupiravir was prescribed in 1.9% of the COVID-19 patients (low risk = 0.1%, moderate risk = 5.8%, high risk = 6.9%). Conclusions Nirmatrelvir/ritonavir and molnupiravir were poorly used in the treatment of adult COVID-19 patients in Taiwan during the pandemic in 2022, especially in moderate-to-high risk groups for progression to severe COVID-19. [ABSTRACT FROM AUTHOR]

Background Positive viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cultures indicate shedding of infectious virus and corresponding transmission risk of coronavirus disease 2019 (COVID-19). The research question of this systematic review was: Is there a discernible pattern in the timing of SARS-CoV-2 virus isolation, and what is the proportion of positive and negative results for isolation of SARS-CoV-2 virus with viral culture relative to the onset of clinical symptoms or the day of diagnosis, as indicated by longitudinal studies? Methods We systematically searched PubMed and Embase from inception to 16 February 2023 for English-language studies with serial viral culture testing within symptomatic or asymptomatic SARS-CoV-2 infected persons during the post-vaccination period. Outcomes of interest were the daily culture status per study and the overall daily culture positivity rate of SARS-CoV-2. We critically appraised the selected studies using the Newcastle-Ottawa quality assessment scale. Results We included 14 viral shedding studies in this systematic review. Positive viral SARS-CoV-2 cultures were detected in samples ranging from 4 days before to 18 days after symptom onset. The daily culture SARS-CoV-2 positivity rate since symptom onset or diagnosis showed a steep decline between day 5 and 9, starting with a peak ranging from 44% to 50% on days −1 to 5, decreasing to 28% on day 7 and 11% on day 9, and finally ranging between 0% and 8% on days 10–17. Conclusions Viral shedding peaked within 5 days since symptom onset or diagnosis and the culture positivity rate rapidly declined hereafter. This systematic review provides an overview of current evidence on the daily SARS-CoV-2 culture positivity rates during the post-vaccination period. These findings could be used to estimate the effectiveness of public health control measures, including treatment and preventive strategies, to reduce the spread of COVID-19. [ABSTRACT FROM AUTHOR]

Background Data on paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited, especially from the early pandemic period. Moreover, children are not considered to be at high risk for severe outcomes of coronavirus disease 2019 (COVID-19). In this systematic review and meta-analysis, we estimated the SAR-CoV-2 positivity rate, identified risk factors, and described the severity and mortality outcomes of SARS-CoV-2 infections in children aged ≤18 years until December 2021, prior to the Omicron era. Methods We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and the World Health Organization (WHO) COVID-19 global literature databases for primary studies recruiting children aged ≤18 years with a diagnosis of SARS-CoV-2 infection confirmed either by molecular or antigen tests. We used the Joanna Briggs Institute critical appraisal tools to appraise the study quality and conducted meta-analyses using the random effects model for all outcomes except for race/ ethnicity as risk factors of SARS-CoV-2 infection. Results We included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9.30% (95% confidence interval (CI)=7.15–11.73). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (risk ratio (RR)=1.33; 95% CI=1.04–1.71) based on data from 49 studies. Most cases in this review presented with mild disease (n=50; 52.47% (95% CI=44.03–60.84)). However, 20.70% of paediatric SARS-CoV-2 infections were hospitalised (67 studies), 7.19% required oxygen support (57 studies), 4.26% required intensive care (93 studies), and 2.92% required assisted ventilation (63 studies). The case fatality ratio (n=119) was 0.87% (95% CI=0.54–1.28), which included in-hospital and out-of-hospital deaths. Conclusions Our data showed that children were at risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for the paediatric population to protect against the acute and long-term sequelae of COVID-19. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccines adapted to newly emerging circulating variants are necessary to better protect the population due to the evolving nature of the SARS-CoV-2 virus. Research Design and Methods: The South African population was stratified by age and risk (defined by comorbidities such as diabetes, obesity, smoking, cancer, and asthma), and HIV status. The outcomes of different vaccination strategies based on age, risk, and HIV status were estimated using a Markov-decision tree model based on age-specific inputs derived from the literature and South African surveillance data. Results: Vaccinating older adults and those with comorbidities was estimated to avert 111,179 infections 18,281 hospitalizations, and 3,868 deaths, resulting in savings of ZAR 1,260 million (USD 67 million) and ZAR 3,205 million (USD 170 million) in direct and indirect costs, respectively. Similar results were obtained when considering strategies targeting older adults and the HIV population. Expanding vaccination to 75% of the standard-risk population prevented more infections (401%), hospitalizations (167%), and deaths (67%) and increased the direct (232%) and indirect (455%) cost savings compared to the base case. Conclusions: Implementing widespread vaccination strategies that utilize a vaccine adapted to the prevailing circulating variant in South Africa would result in significant public health and economic gains. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore. Research Design and Methods: The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. Results: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case. Conclusions: Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore. [ABSTRACT FROM AUTHOR]

Vaccination against infectious disease affords direct protection from vaccine-induced immunity and additional indirect protection for unvaccinated persons. A systematic review was conducted to estimate the indirect effect of COVID-19 vaccination. From PubMed and Embase, 31 studies were included describing the impact of original wild-type COVID-19 vaccines on disease transmission or viral load. Overall, study results showed the effectiveness of COVID-19 vaccination against SARS-CoV-2 transmission (range 16–95%), regardless of vaccine type or number of doses. The effect was apparent, but less pronounced against omicron (range 24–95% for pre-omicron variants versus 16–31% for omicron). Results from viral load studies were supportive, showing SARS-CoV-2 infections in vaccinated individuals had higher Ct values, suggesting lower viral load, compared to infections among the unvaccinated. Based on these findings, well-timed vaccination programs may help reduce SARS-CoV-2 transmission—even in the omicron era. Whether better-matched vaccines can improve effectiveness against transmission in the omicron era needs further study. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The EMPA‐REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all‐cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries. Materials and Methods: The study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase‐4 inhibitors (DPP‐4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score‐matched (1:1) 'as‐treated' analyses comparing the risk of cardiovascular outcomes and all‐cause mortality between empagliflozin and DPP‐4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta‐analysis models comparing both empagliflozin and SGLT2i with DPP‐4i use, respectively. Intention‐to‐treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed. Results: The study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP‐4i and SGLT2i/DPP‐4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all‐cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67–0.86) and SGLT2i (0.71, 0.65–0.77); (ii) combined myocardial infarction, stroke, and all‐cause mortality was also lower with empagliflozin (0.74, 0.61–0.88) and SGLT2i (0.69, 0.60–0.78) compared to DPP‐4i. The intention‐to‐treat and three subgroup analyses were consistent with results of the main analyses. Conclusions: The results suggest that both empagliflozin and SGLT2i compared with DPP‐4i are associated with a lower risk of cardiovascular events and all‐cause mortality in routine clinical care in East Asia. [ABSTRACT FROM AUTHOR]

Background With the emergence of new variants and sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reinfections can significantly impact herd immunity, vaccination policies, and decisions on other public health measures. We conducted a systematic review and meta-analysis to synthesise the global evidence on SARS-CoV-2 reinfections in the pre-Omicron era. Methods We searched five global databases (MEDLINE, Embase, CINAHL Plus, Global Health, WHO COVID-19) on 12 May 2022 and 28 July 2023 and three Chinese databases (CNKI, Wanfang, CQvip) on 16 October 2022 for articles reporting incidence and outcomes of SARS-CoV-2 reinfection before the period of Omicron (B.1.1.529) predominance. We assessed risk of bias using Joanna Briggs Institute critical appraisal tools and conducted meta-analyses with random effects models to estimate the proportion of SARS-CoV-2 reinfection among initially infected cases and hospitalisation and mortality proportions among reinfected ones. Results We identified 7593 studies and extracted data from 64 included ones representing 21 countries. The proportion of SARS-CoV-2 reinfection was 1.16% (95% confidence interval (CI) = 1.01-1.33) based on 11 639 247 initially infected cases, with ≥45 days between the two infections. Healthcare providers (2.28%; 95% CI = 1.37-3.40) had a significantly higher risk of reinfection than the general population (1.00%; 95% CI = 0.81-1.20), while young adults aged 18 to 35 years (1.01%; 95% CI = 0.8-1.25) had a higher reinfection burden than other age groups (children <18 years old: 0.57%; 95% CI = 0.39-0.79, older adults aged 36-65 years old: 0.53%; 95% CI = 0.41-0.65, elderly >65 years old: 0.37%; 95% CI = 0.15-0.66). Among the reinfected cases, 8.12% (95% CI = 5.30-11.39) were hospitalised, 1.31% (95% CI = 0.29-2.83) were admitted to the intensive care unit, and 0.71% (95% CI = 0.02-2.01) died. Conclusions Our data suggest a relatively low risk of SARS-CoV-2 reinfection in the pre-Omicron era, but the risk of hospitalisation was relatively high among the reinfected cases. Considering the possibility of underdiagnosis, the reinfection burden may be underestimated. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. This study aimed to examine clinical characteristics, overall vaccine uptake, and to assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. A nationwide retrospective study was conducted using various Brazilian databases including, COVID-19 related databases, public health systems, and other surveillance/demographic datasets. Individuals with positive COVID-19 test results between January 1 2022 and April 30 2022, during Omicron BA.1/BA.2 wave, were identified. Patients' demographics, vaccine uptake, HCRU and corresponding costs were described by age groups. A total of 8,160,715 (3.80%) COVID-19 cases were identified in the study cohort, ranging from 2.43% in <5 years to 62.05% in 19-49 years. The uptake of partial (Dose 1) or full immunization (Dose 2) was less than 0.1% in children aged <5 years, whereas in individuals ≥ 19 years, it exceeded 89.78% for Dose 1 and 84.07% for Dose 2. Overall booster vaccine uptake was 38.06%, which was significantly higher among individuals aged ≥ 65 years, surpassing 74.79%. Regardless of vaccination status, 87.2% cases were symptomatic, and 1.48% were hospitalized due to acute COVID-19 (<5 years: 2.33%, 5-11 years: 0.99%, 12-18 years: 0.32%, 19-49 years: 0.40%; 50-64 years: 1.50%, 65-74 years: 5.43%, and ≥ 75 years: 17.89%). Among the hospitalized patients (n = 120,450), 32.57% were admitted to ICU, of whom 31,283 (79.75%) individuals required mechanical ventilation (MV) support. The average cost per day in normal ward and ICU without MV in public/general hospital settings was $104.36 and $302.81, respectively. While average cost per day in normal ward and ICU with MV was $75.91 and $301.22 respectively. This study quantified the burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand. The outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case. Broader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) case numbers have increased following the emergence of the Omicron variant. This study estimated the impact of introducing and increasing the coverage of an Omicron-adapted bivalent booster vaccine in Malaysia. A combined cohort Markov decision tree model was used to compare booster vaccination with an Omicron-adapted bivalent COVID-19 vaccine versus no booster vaccination in Malaysia. The model utilized age-specific data from January 2021 to March 2022 derived from published sources. The outcomes of interest included case numbers, hospitalizations, deaths, medical costs, and productivity losses. The population was stratified into high-risk and standard-risk subpopulations, and the study evaluated the benefits of increased coverage in different age and risk groups. Vaccinating only high-risk individuals and those aged ≥ 65 years was estimated to avert 274,313 cases, 33229 hospitalizations, 2,434 deaths, Malaysian ringgit (MYR) 576 million in direct medical costs, and MYR 579 million in indirect costs. Expanding vaccination coverage in the standard-risk population to 75% was estimated to avert more deaths (31%), hospitalizations (155%), infections (206%), direct costs (206%), and indirect costs (281%). These findings support broader population Omicron-adapted bivalent booster vaccination in Malaysia with potential for significant health and economic gains. [ABSTRACT FROM AUTHOR]

Limited data are available describing the global impact of COVID-19 vaccines. This study estimated the global public health and economic impact of COVID-19 vaccines before the emergence of the Omicron variant. A static model covering 215 countries/territories compared the direct effects of COVID-19 vaccination to no vaccination during 13 December 2020–30 September 2021. After adjusting for underreporting of cases and deaths, base case analyses estimated total cases and deaths averted, and direct outpatient and productivity costs saved through averted health outcomes. Sensitivity analyses applied alternative model assumptions. COVID-19 vaccines prevented an estimated median (IQR) of 151.7 (133.7–226.1) million cases and 620.5 (411.1–698.1) thousand deaths globally through September 2021. In sensitivity analysis applying an alternative underreporting assumption, median deaths averted were 2.1 million. Estimated direct outpatient cost savings were $21.2 ($18.9–30.9) billion and indirect savings of avoided productivity loss were $135.1 ($121.1–206.4) billion, yielding a total cost savings of $155 billion globally through averted infections. Using a conservative modeling approach that considered direct effects only, we estimated that COVID-19 vaccines have averted millions of infections and deaths, generating billions of cost savings worldwide, which underscore the continued importance of vaccination in public health response to COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Real-world data on COVID-19 vaccine effectiveness are needed to validate evidence from randomized clinical trials. Accordingly, this study aims to evaluate, in a real-world setting in Brazil, the effectiveness of Pfizer-BioNTech BNT162b2 against symptomatic COVID-19 and COVID-19-related complications across diverse populations. Materials and methods: A test-negative case-control study with follow-up of cases is currently being conducted in Toledo, a city in southern Brazil, following a mass COVID-19 vaccination campaign with BNT162b2. The study is being conducted among patients aged 12 years or older seeking care in the public health system with acute respiratory symptoms and tested for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). Cases are RT-PCR positive and controls RT-PCR negative. Test-positive cases are prospectively followed through structured telephone interviews performed at 15 days post-enrollment, and at 1, 3, 6, 9 and 12 months. Baseline demographic, clinical, and vaccination data are being collected by means of structured interviews and medical registry records reviews at the time of enrollment. All RT-PCR-positive samples are screened for mutations to identify SARS-CoV-2 variants. Ethics and dissemination: The study protocol has been approved by the research ethics committee of all participant sites. Study findings will be disseminated through peer-reviewed publications and conference presentations. Trail registration: Clinicatrials.gov:NCT05052307. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We investigated the utilization of healthcare resources in patients with type 2 diabetes treated with empagliflozin, a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor, versus dipeptidyl peptidase‐4 (DPP‐4) inhibitors in clinical practice in Japan, South Korea, and Taiwan. Materials and Methods: We analyzed the Japanese Medical Data Vision database (December 2014–April 2018), the South Korean National Health Information Database, and the Taiwanese National Health Insurance claims database (both May 2016–December 2017). Patients with type 2 diabetes starting empagliflozin, 10 or 25 mg, or a DPP‐4 inhibitor were matched 1:1 via propensity scores (PS). We compared inpatient care needs, emergency room (ER) visits, and outpatient visits between the treatment groups using Poisson regression and Cox proportional hazards models, pooled across countries by random‐effects meta‐analysis. Results: We identified 28,712 pairs of PS‐matched patients; the mean follow‐up was 5.7–6.8 months. Empagliflozin‐treated patients had a 27% lower risk of all‐cause hospitalization compared with DPP‐4 inhibitor–treated patients (rate ratio [RR] 0.73, 95% CI 0.67–0.79), and 23% reduced risk for first hospitalization (hazard ratio 0.77, 95% CI 0.73–0.81). The risk for an ER visit was 12% lower with empagliflozin than with DPP‐4 inhibitors (RR 0.88, 95% CI 0.83–0.94) while the risk for outpatient visit was 4% lower (RR 0.96, 95% CI 0.96–0.97). These findings were generally consistent across countries, regardless of baseline cardiovascular disease, and in the subgroup starting empagliflozin with the 10 mg dose. Conclusions: Empagliflozin treatment was associated with lower inpatient care needs and other healthcare resource utilization than DPP‐4 inhibitors in routine clinical practice in East Asia in this study. [ABSTRACT FROM AUTHOR]

Background and Aim: The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. Methods: This is a case–control study of prospectively collected data from a territory‐wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. Results: Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. Conclusion: In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region‐specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC. [ABSTRACT FROM AUTHOR]

Background Nasopharyngeal pneumococcal carriage (NPC) is a prerequisite for invasive pneumococcal disease and reduced carriage of vaccine serotypes is a marker for the protection offered by the pneumococcal conjugate vaccine (PCV). The present study reports NPC during the first year of life in a vaccinated (with PCV10) cohort in Bangladesh and an unvaccinated cohort in India. Methods A total of 450 and 459 infants were recruited from India and Bangladesh respectively within 0-7 days after birth. Nasopharyngeal swabs were collected at baseline, 18 and 36 weeks after birth. The swabs were processed for pneumococcal culture and identification of serotypes by the Quellung test and polymerase chain reaction (PCR). An identical protocol was applied at both sites. Results Prevalence of NPC was 48% in the Indian and 54.8% in the Bangladeshi cohort at 18 weeks. It increased to 53% and 64.8% respectively at 36 weeks. The average prevalence of vaccine serotypes was higher in the Indian cohort (17.8% vs 9.8% for PCV-10 and 26.1% vs17.6% for PCV-13) with 6A, 6B, 19F, 23F, and 19A as the common serotypes. On the other hand, the prevalence of non-vaccine serotypes was higher (43.6% vs 27.1% for non-PCV13) in the Bangladeshi cohort with 34, 15B, 17F, and 35B as the common serotypes. Overcrowding was associated with increased risk of pneumococcal carriage. The present PCV-13 vaccine would cover 28%-30% and 47%-48% serotypes in the Bangladeshi and Indian cohorts respectively. Conclusions South Asian infants get colonised with pneumococci early in infancy; predominantly vaccine serotypes in PCV naïve population (India) and non-vaccine serotypes in the vaccinated population (Bangladesh). These local findings are important to inform the public health policy and the development of higher valent pneumococcal vaccines. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study. Materials and methods: Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end‐stage renal disease (ESRD) and all‐cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random‐effects meta‐analysis. Results: Overall, 28 712 pairs of PS‐matched patients were identified with mean follow‐up of 5.7‐6.8 months. Compared with DPP‐4 inhibitors, the risk of HHF was reduced by 18% and all‐cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71‐0.94, and HR 0.64; 95% CI 0.50‐0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP‐4 inhibitors (HR 0.37; 95% CI 0.24‐0.58). Conclusions: Empagliflozin treatment was associated with reduced risk for HHF, all‐cause mortality and ESRD compared with DPP‐4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan. [ABSTRACT FROM AUTHOR]

Background: Respiratory Syncytial Virus (RSV) is one of the most frequent causes of acute respiratory infection worldwide. Understanding age-specific health care utilization is necessary to guide effective prevention strategies. This retrospective database analysis assessed the incidence rates of RSV-related health care utilization in the USA over a 7-year period.Methods: Episodes of RSV were identified in the Truven Health MarketScan® Commercial Claims and Encounters database between 2008 and 2014 using ICD-9-CM codes for pneumonia, bronchiolitis and RSV (480-486, 487.0, 466.1, 491.2, 079.6). Annual RSV-related health care utilization was calculated for the total population, by age group (<1, 1, 2-4, 5-17, 18-49, 50-64, 65-74, 75-84 and ≥85 years) and the proportion of cases for each setting (hospitalization, outpatient, or emergency department [ED] / urgent care [UC]).Results: Over the 7-year study period, the mean rate of all RSV-associated health care utilization was 2.4 per 1000 person-years, with mean rates ranging from 2.0 to 2.6). The highest rate was seen in infants aged <1 year (mean 79.0 per 1000 over the 7-year period), which decreased with increasing age in the range 2-49 years before increasing with age in older adults (mean rate 8.1 per 1000 over the 7-year period in those ≥85 years). Of all RSV cases, 82% were reported in an outpatient setting, 11% in the ED/UC and 7% were hospitalized.Conclusions: The annual RSV-related healthcare utilization rates were substantial, especially in infants and young children. These results underscore the need to accelerate the development of RSV prevention strategies to reduce the healthcare burden of RSV. [ABSTRACT FROM AUTHOR]

Background and Aim: Secondary prophylaxis (SP) of variceal rebleeding was reported to improve outcomes of hepatocellular carcinoma (HCC) patients, but the optimal endoscopic approach is not well defined. We compared outcomes in HCC patients who underwent SP by endoscopic ultrasound‐guided cyanoacrylate obturation (EUS‐CYA) versus no SP. Methods: Between 2014 and 2018, 30 consecutive patients with inoperable HCC and recent endoscopically controlled variceal bleeding were prospectively recruited. Twenty‐seven patients with persistent varices ≥ 3 mm on endoscopic ultrasound underwent EUS‐CYA for SP. Thirty‐three HCC patients treated by esophagogastroduodenoscopy‐guided CYA obturation (EGD‐CYA) alone for acute variceal bleeding between 2009 and 2013 were identified from a prospective gastrointestinal bleed registry as standard of care controls for comparison. Outcome measures were death‐adjusted cumulative incidence of rebleeding, bleeding‐free survival, technical success, and procedure‐related adverse events of EUS‐CYA. Results: The majority of patients in both groups had advanced HCC, portal vein thrombosis, and Child–Pugh B cirrhosis. EUS‐CYA was successful in all 27 patients with no radiographic evidence of cyanoacrylate–lipiodol embolization. Significantly lower 30‐ and 90‐day death‐adjusted cumulative incidence of rebleeding (14.8% vs 42.4%, P = 0.023 and 18.5% vs 60.6%, P = 0.002, respectively) and significantly higher variceal bleeding‐free survival at 3 and 6 months (51.9% vs 21.2%, P = 0.009, 40.7% vs 15.2%, P = 0.010, respectively) were observed in the EUS‐CYA group when compared with standard of care group. Conclusions: Secondary prophylaxis by EUS‐CYA reduced rebleeding rate and improved variceal bleeding‐free survival in patients with inoperable HCC and variceal bleeding when compared with no SP. Randomized studies are needed to confirm the benefits of EUS‐CYA for this difficult‐to‐treat population. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years.Methods: We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases.Results: We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event.Conclusions: Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society. [ABSTRACT FROM AUTHOR]

Background The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes. Methods We identified consecutive annual (July–June) cohorts of Tennessee Medicaid–enrolled children (2006–2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)–era (2006–2010) and PCV13-era (2011–2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts. Results We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013–2014 cohort compared with the 2009–2010 cohort (aHRs [95% confidence interval], 0.92 [.91–.93] and 0.76 [.72–.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM. Conclusions The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes. [ABSTRACT FROM AUTHOR]

Background: Meningococcal disease is caused by the bacteria Neisseria meningitidis, leading to substantial mortality and severe morbidity; with serogroups A, B, C, W135, X and Y most significant in causing disease. An outbreak is defined as multiple cases of the same serogroup occurring in a population over a short time-period. A systematic review was performed to gain insight into outbreaks of meningococcal disease and to describe the temporal pattern over the last 50 years in non-African countries.Methods: PubMed and EMBASE were searched for English-language publications on outbreaks of meningococcal disease in non-African countries between January 1966 and July 2017, with an additional grey literature search. Articles and reports were considered eligible if they reported confirmed meningococcal outbreak cases, included the region, number of cases, and the start and end dates of the outbreak. Data on outbreaks was stratified by geographical region in accordance with the World Health Organization (WHO) regional classification, and case-fatality rates (CFRs) were calculated.Results: Of the identified publications, 3067 were screened and 73 included, reporting data from 83 outbreaks. The majority of outbreaks were identified in the regions of the Americas (41/83 outbreaks), followed by the European region (30/83 outbreaks). In each of the Western Pacific, Eastern Mediterranean, and South-East Asian regions there were <10 outbreaks reported. The predominant serogroup in the majority of outbreaks was serogroup C (61%), followed by serogroup B (29%), serogroup A (5%) and serogroup W135 (4%). Outbreaks showed a peak in the colder months of both the Northern and Southern Hemispheres. Of the 54 outbreaks where CFR was calculable for all outbreak cases, it ranged from 0%-80%.Conclusions: These data present a retrospective view of the patterns for meningococcal disease outbreaks in non-African countries, and provide valuable data for monitoring future changes in disease epidemiology and informing preventive measures. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates.Methods: Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model.Results: 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups.Conclusions: Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community. [ABSTRACT FROM AUTHOR]

Background: Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on circulating meningococcal serogroups have never been reviewed concurrently with the laboratory capacity for meningococcal surveillance at the national level. We, therefore, aimed to conduct a country-level review of meningococcal surveillance, serogroup distribution, and vaccine use.Methods: We conducted a systematic literature review across six databases to identify studies (published January 1, 2010 to October 16, 2017) and grey literature reporting meningococcal serogroup data for the years 2010-2016. We performed independent random effects meta-analyses for serogroups A, B, C, W, X, Y, and other. We developed and circulated a questionnaire-based survey to surveillance focal points in countries (N = 95) with known regional bacterial meningitis surveillance programs to assess their surveillance capacity and summarized using descriptive methods.Results: We included 173 studies from 59 countries in the final analysis. The distribution of meningococcal serogroups differed markedly between countries and regions. Meningococcal serogroups C and W accounted for substantial proportions of meningococcal disease in most of Africa and Latin America. Serogroup B was the predominant cause of meningococcal disease in many locations in Europe, the Americas, and the Western Pacific. Serogroup Y also caused many cases of meningococcal disease in these regions, particularly in Nordic countries. Survey responses were received from 51 countries. All countries reported the ability to confirm the pathogen in-country, while approximately 30% either relied on reference laboratories for serogrouping (N = 10) or did not serogroup specimens (N = 5). Approximately half of countries did not utilize active laboratory-based surveillance system (N = 22). Nationwide use of a meningococcal vaccine varied, but most countries (N = 36) utilized a meningococcal vaccine at least for certain high-risk population groups, in private care, or during outbreaks.Conclusions: Due to the large geographical variations in circulating meningococcal serogroups, each country should continue to be monitored for changes in major disease-causing serogroups in order to inform vaccine and control policies. Similarly, laboratory capacity should be appropriately scaled up to more accurately understand local epidemiology and disease burden, as well as the impact of vaccination programs. [ABSTRACT FROM AUTHOR]

Objective Neisseria meningitidis carriage prevalence has known variation across the lifespan, but it is unclear whether carriage varies among meningococcal capsular groups. Therefore, we aimed to characterise group-specific meningococcal carriage by age group and world region from 2007 to 2016. Design Systematic review and meta-analysis. Data sources MEDLINE, Embase, Global Health Database, WHO Global Health Library, Web of Science, Current Contents Connects, China National Knowledge Infrastructure and Wanfang were systematically searched. Database searches were conducted through July 2018 and Google Scholar forward searches of included studies were conducted through August 2018. References of included studies and relevant conference abstracts were also searched to identify additional articles for inclusion. Eligibility criteria Studies were eligible for inclusion if they reported capsular group-specific meningococcal carriage in a healthy population of a specified age group and geographical region. For this review, only studies conducted between 2007 and 2016 were included. Data extraction and synthesis Data were independently extracted by two authors into Microsoft Access. Studies were assessed for risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Studies eligible for inclusion in quantitative analyses by pre-specified age groups were pooled using random effects meta-analyses. Results are reported by capsular group, age group and WHO region. Where meta-analyses were not appropriate, study results were discussed narratively. Results 7511 articles were identified and 65 were eligible for inclusion. Adolescents and young adults were the focus of many studies (n=24), especially in the Americas and Europe. Studies from China and Africa, typically, included data from a wider age range. The overall carriage prevalence varied markedly by age group and region. Based on the available data, 21 studies were included in meta-analyses reporting serogroup carriage for: all ages in Africa, 18-24-year olds in the Americas, and 11-17 and 18-24-year olds in Europe. Capsular groups W, X, Y and 'other' (non-ABCWXY, including non-groupable) were the most prevalent in Africa, and 5-17-year olds had higher carriage prevalence than other age groups. 'Other' serogroups (11.5%, 95% CI 1.6% to 16.1%) were the most common among 18-24-year olds from the Americas. In Europe, 18-24-year old were carriers more frequently than 11-17-year olds, and groups B (5.0%, 95% CI 3.0% to 7.5%), Y (3.9%, 95% CI 1.3% to 7.8%) and 'other' (6.4%, 95% CI 3.1% to 10.8%) were the most commonly carried in the older age group. Conclusions Of the age groups included in the analysis, carriage patterns by age were similar across capsular groups within a region but differed between regions. Data gaps remain for age- and capsular group-specific carriage in many regions, especially in the Eastern Mediterranean and South-East Asia. As such, clear and robust conclusions about the variation of capsular group-specific carriage by age group and WHO region were unable to be determined. PROSPERO registration number CRD42017074671. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1–41.2% and 9.1–36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the ‘all children’ group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1–5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions. A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI.Methods: We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016.Results: 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis.Conclusion: Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research. [ABSTRACT FROM AUTHOR]

Background: Routine immunisation with pneumococcal conjugate vaccines (PCV7/10/13) has reduced invasive pneumococcal disease (IPD) due to vaccine serotypes significantly. However, an increase in disease due to non-vaccine types, or serotype replacement, has been observed. Serotypes’ individual contributions to IPD play a critical role in determining the overall effects of PCVs. This study examines the distribution of pneumococcal serotypes in children to identify leading serotypes associated with IPD post-PCV introduction. Methods: A systematic search was performed to identify studies and surveillance reports (published between 2000 and December 2015) of pneumococcal serotypes causing childhood IPD post-PCV introduction. Serotype data were differentiated based on the PCV administered during the study period: PCV7 or higher valent PCVs (PCV10 or PCV13). Meta-analysis was conducted to estimate the proportional contributions of the most frequent serotypes in childhood IPD in each period. Results: We identified 68 studies reporting serotype data among IPD cases in children. We analysed data from 38 studies (14 countries) where PCV7 was administered and 20 (24 countries) where PCV10 or PCV13 have been introduced. Studies reported early and late periods of PCV7 administration (range: 2001∓13). In these settings, serotype 19A was the most predominant cause of childhood IPD, accounting for 21.8% (95%CI 18.6∓25.6) of cases. In countries that have introduced higher valent PCVs, study periods were largely representative of the transition and early years of PCV10 or PCV13. In these studies, the overall serotype-specific contribution of 19A was lower (14.2% 95%CI 11.1∓18.3). Overall, non-PCV13 serotypes contributed to 42.2% (95%CI 36.1∓49.5%) of childhood IPD cases. However, regional differences were noted (57.8% in North America, 71.9% in Europe, 45.9% in Western Pacific, 28.5% in Latin America, 42.7% in one African country, and 9.2% in one Eastern Mediterranean country). Predominant non-PCV13 serotypes overall were 22F, 12F, 33F, 24F, 15C, 15B, 23B, 10A, and 38 (descending order), but their rank order varied by region. Conclusion: Childhood IPD is associated with a wide number of serotypes. In the early years after introduction of higher valent PCVs, non-PCV13 types caused a considerable proportion of childhood IPD. Serotype data, particularly from resource-limited countries with high burden of IPD, are needed to assess the importance of serotypes in different settings. The geographic diversity of pneumococcal serotypes highlights the importance of continued surveillance to guide vaccine design and recommendations. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance.Methods: We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines.Results: We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality.Conclusion: Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations. [ABSTRACT FROM AUTHOR]

Background Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in children and young adults worldwide. The disease burden associated with N. meningitidis infections has not been systematically assessed in China. Therefore, we undertook this study to determine the burden of meningococcal disease in China. Method We performed a systematic review and meta-analysis of articles on N. meningitidis incidence, carriage, seroprevalence and mortality rates in China by searching the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed for publications from January 2005 to Aug 2015. Results In total, 50 articles were included in our analysis. The overall incidence of meningococcal disease and associated mortality were estimated to be 1.84 (95% confidence interval (CI) 0.91-3.37) per 100 000 persons per year and 0.33 (95% CI 0.12-0.86) per 100 000 persons per year, respectively. N. meningitidis carriage rate among the healthy population was estimated to be 2.7% (95% CI 2.0-3.5%). Prevalence of antibodies against N. meningitidis serogroup A and C were estimated to be 77.3% (95% CI 72.4%-81.6%) and 33.5% (95% CI 27.0%-40.8%), respectively. No studies were found for serogroup specific disease burden. Conclusions The overall incidence of meningococcal disease in China is low. The lower seroprevalence of serogroup C within the population suggests that it may pose a greater risk for meningococcal disease outbreak than serogroup A. The lack of data on serogroup disease burden by age groups suggests the implementation of laboratory based meningococcal surveillance systems are urgently needed in China. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain.Methods: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation.Results: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay.Conclusions: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus and Pseudomonas aeruginosa are major causes of pneumonia in intensive care unit (ICU) patients. Limited data exist regarding the health economic impact of S. aureus and P. aeruginosa pneumonias in the ICU setting. Methods: We conducted a retrospective observational cohort study using a 29.6 million enrollee US medical and pharmacy administrative claims database. ICU patients with S. aureus or P. aeruginosa infection per International Classification of Diseases, 9th ed. coding between 01/01/2007-8/31/2012 were compared with ICU patients without any pneumonia or infections of interest. Primary outcomes were costs in 2012 US dollars, healthcare utilization and all-cause mortality associated with hospital-acquired S. aureus or P. aeruginosa pneumonia, and the relative odds of incurring higher costs due to a comorbid condition. Results: Patients with S. aureus or P. aeruginosa pneumonia had longer mean hospital (37.9 or 55.4 vs 7.2 days, P < .001) and ICU stays (6.9 or 14.8 vs 1.1 days, P < .001), a higher rate of mechanical ventilation (62.6 % or 62.3 % vs 7.4 %, P < .001), higher mortality (16.0 % or 20.2 % vs 3.1 %, P < .001), and higher total mean hospitalization costs ($146,978 or $213,104 vs $33,851, P < .001) vs controls. Pneumonia survivors had significantly increased risk of rehospitalization within 30 days (27.2 % or 31.1 % vs 15.3 %, P < .001). Comorbid conditions were not associated with increased cost in the pneumonia cohorts. Conclusions: Healthcare costs and resource utilization were high among ICU patients with S. aureus or P. aeruginosa pneumonia. Reducing the incidence of these infections could lead to substantial cost savings in the United States. [ABSTRACT FROM AUTHOR]

Background. In 2006, a mumps outbreak occurred on a university campus despite ≤ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients). Methods. Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA). Results. Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P = .023), and EIA results were significantly lower among case patients than exposed nonpatients (P = .007) and unexposed nonpatients (P = .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti-Jeryl Lynn titer< 31 (64% vs 27%, respectively; P = .065), an anti-Iowa-G/ USA-06 titer < 8 (55% vs 14%; P = .033), and EIA index standard ratio <1.40 (64% vs 9%; P = .002) and < 1.71 (73% vs 14%, P = .001). Discussion. Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients. [ABSTRACT FROM AUTHOR]

The 2006 mumps resurgence in the United States raised questions about the appropriate isolation period for people with mumps. To determine the scientific basis for isolation recommendations, we conducted a literature review and considered isolation of virus and virus load in saliva and respiratory secretions as factors that were related to mumps transmission risk. Although mumps virus has been isolated from 7 days before through 8 days after parotitis onset, the highest percentage of positive isolations and the highest virus loads occur closest to parotitis onset and decrease rapidly thereafter. Most transmission likely occurs before and within 5 days of parotitis onset. Transmission can occur during the prodromal phase and with subclinical infections. Updated guidance, released in 2007-2008, changed the mumps isolation period from 9 to 5 days. It is now recommended that mumps patients be isolated and standard and droplet precautions be followed for 5 days after parotitis onset. [ABSTRACT FROM AUTHOR]

Background: High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure.Methods: Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for < or =5 years and > or =15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration.Results: Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 (P = .568). The geometric mean titer (GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 (95% CI, 64-148), whereas, among those vaccinated > or =15 years before blood collection, the GMT was 58 (95% CI, 44-76) (P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively.Conclusions: Lower levels of NA observed among persons who received MMR2 > or =15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response. [ABSTRACT FROM AUTHOR]

Background. High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure. Methods. Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for ⩽5 years and ⩾15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration. Results. Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 (P = .568). The geometric mean titer (GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 (95% CI, 64-148), whereas, among those vaccinated ⩾15 years before blood collection, the GMT was 58 (95% CI, 44-76) (P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively. Conclusions. Lower levels of NA observed among persons who received MMR2 ⩾15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response. [ABSTRACT FROM AUTHOR]

Background. Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. Methods. This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. Results. Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were ~5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). Conclusions. Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants. [ABSTRACT FROM AUTHOR]

Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (≥18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons. [ABSTRACT FROM AUTHOR]

A record linkage study was done to provide comprehensive data on the epidemiologic characteristics of invasive pneumococcal disease (IPD) in Scotland. The overall incidence of IPD was 11 cases/10[sup5] persons and 21 cases/10[sup5] persons <1 year of age, 51 cases/10[sup5] persons 1 year of age, 45 cases/10[sup5] elderly persons (age ≥65 years), 176–483 cases/10[sup5] persons with chronic medical conditions, and 562–2031 cases/10[sup5] persons with severe immunosuppression. The case-fatality rate was 11% among elderly persons and ranged from 3% to 13% among persons with underlying medical conditions. The most common pneumococcal serogroups associated with IPD were 14, 9, 6, 19, 23, 8, and 4. Serogroups included in the 23-valent polysaccharide vaccine caused the majority of cases of IPD. The proportion of IPD due to the 7­, 9­, and 11­valent conjugate vaccine serogroups was lower among older people and persons with underlying medical conditions. [ABSTRACT FROM AUTHOR]

Penicillin resistance of Pneumococci is a problem in several European countries. Therefore, we examined 510 invasive pneumococcal isolates, collected between 1992 and 1999 via a national network of diagnostic laboratories covering the entire population of Scotland, for penicillin susceptibility, in order to determine the prevalence, site of infection and serogroup/type distribution of penicillin-resistant Pneumococci in the elderly (≥ 65 y). Of the 510 isolates, 91.6% (n = 467) were from blood, 4.7% (n = 24) from other sterile sites and 3.7% (n = 19) from cerebrospinal fluid. The prevalence of penicillin non-susceptible isolates during the study period was 9%. An increase in the proportion of Pneumococci non-susceptible to penicillin was detected from 1996 onwards, from 10.8% in 1996 to 14.3% in 1999. There were 2 isolates with high-level penicillin resistance, both of which were of serotype 14, accounting for 4.3% (2/46) of all non-susceptible isolates. Penicillin non-susceptible isolates belonged to the following serogroups: 14 (32.6%); 9 (30.4%); 6 (19.6%); 23 (10.9%); and 19 (6.5%). The leading non-susceptible serotype/group varied according to the specimen type: serotype 14 for blood and serogroup 9 for all other sterile sites. Current polysaccharide and new 7-, 9- and 11-valent conjugate vaccine formulations included the serogroups responsible for all the penicillin non-susceptible isolates detected. Therefore vaccination represents the most effective strategy for decreasing the burden of drug resistance. Constant surveillance of the patterns of antibiotic non-susceptible isolates, the site of infection and the serogroup/type are necessary in order to select antibiotic therapy and establish vaccination policy for the prevention of invasive pneumococcal disease. [ABSTRACT FROM AUTHOR]