Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial.

Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial.

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

Policy Analysis for Prevention and Control of Influenza in Aged Care.

OBJECTIVE: This study aimed to analyze national influenza infection control policy documents within aged care settings by identifying the consistencies, inconsistencies, and gaps with the current evidence and by evaluating methodological quality. Aged care providers can use these findings to identify their policy documents' strengths and weaknesses. DESIGN: A quality and content analysis of national level policy documents. SETTING AND PARTICIPANTS: Aged care settings rely on national agencies' policy recommendations to control and prevent outbreaks. There is limited research on the effectiveness of control measures to prevent and treat influenza within aged care settings. Because of the complexities around aged care governance, the primary responsibility in developing a comprehensive facility-level, infection-prevention policy, falls to the providers. METHODS: The analysis was conducted using the (1) International Appraisal of Guidelines, Research and Evaluation assessment tool, containing 23 items across 6 domains; and the (2) Influenza Related Control Measures in Aged Care settings checklist, developed by the authors, with 82 recommendations covering: medical interventions, nonmedical interventions, and physical layout. RESULTS: There were 19 documents from 9 different high-income countries, with a moderately high methodological quality in general. The quality assessment's average score was 40.2% (95% CI 31.9%-44.7%). "Stakeholder involvement" ranked third, and "Editorial independence" and "Rigor of development" had the lowest average scores across all domains. The content analysis' average score was 37.2% (95% CI 10.5%-21.5%). The highest scoring document (59.1%) included term definitions, cited evidence for recommendations, and clear measurable instructions. "Physical Layout" had the least coverage and averaged 21.9% (95% CI 4.2%-37.5%), which shows a substantial gap in built environment recommendations. CONCLUSIONS AND IMPLICATIONS: Existing policy documents vary in their comprehensiveness. The higher scoring documents provide an ideal model for providers. The checklist tools can be used to assess and enhance documents. Further research on document end-user evaluation would be useful, as there is room for improvement in methodological quality and coverage of recommendation coverage, especially related to physical layout.

Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively. CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

Epidemiology of paediatric Middle East respiratory syndrome coronavirus and implications for the control of coronavirus virus disease 2019.

AIM: To compare the clinical features of Middle East respiratory syndrome coronavirus (MERS-CoV) infection between paediatric and adult cases. METHODS: Using multiple public data sources, we created an enhanced open-source surveillance dataset of all MERS-CoV cases between 20 September 2012 and 31 December 2018 in Saudi Arabia including available risk factor data. RESULTS: Of the 1791 cases of MERS-CoV identified, 30 cases (1.7%) were aged under 18 years and 1725 cases (96.3%) were aged 18 years and over. Three paediatric cases were fatal, aged 0, 2 and 15 years. The odds of asymptomatic MERS-CoV infection among cases under 18 years (n = 10/23; 44%) was significantly higher (odds ratio (OR) = 4.98; 95% confidence interval (CI): 2.15-11.51; P = 0.001) compared to adults (n = 199/1487; 13%). The odds of hospitalisation were significantly lower (OR = 0.17; 95% CI: 0.08-0.39; P < 0.001) among cases under 18 years (n = 12/24; 50%) compared to adults (n = 1231/1443; 85%). Children were more likely to have a known source of exposure compared to adults (OR = 2.68; 95% CI: 1.29-5.56; P = 0.008). CONCLUSIONS: Clinically severe illness is less common in children, although death can occur, and the proportion of paediatric cases (1.7%) is similar to that reported for COVID-19. Age-specific differences in the clinical presentation of MERS-CoV cases could have implications for transmission for other betacoronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children may be at risk within the household with an infected adult. More studies are required on the role of children in transmission of betacoronaviruses.

Application of a Risk Analysis Tool to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak in Saudi Arabia.

The Grunow-Finke assessment tool (GFT) is an accepted scoring system for determining likelihood of an outbreak being unnatural in origin. Considering its high specificity but low sensitivity, a modified Grunow-Finke tool (mGFT) has been developed with improved sensitivity. The mGFT has been validated against some past disease outbreaks, but it has not been applied to ongoing outbreaks. This study is aimed to score the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia using both the original GFT and mGFT. The publicly available data on human cases of MERS-CoV infections reported in Saudi Arabia (2012-2018) were sourced from the FluTrackers, World Health Organization, Saudi Ministry of Health, and published literature associated with MERS outbreaks investigations. The risk assessment of MERS-CoV in Saudi Arabia was analyzed using the original GFT and mGFT criteria, algorithms, and thresholds. The scoring points for each criterion were determined by three researchers to minimize the subjectivity. The results showed 40 points of total possible 54 points using the original GFT (likelihood: 74%), and 40 points of a total possible 60 points (likelihood: 67%) using the mGFT, both tools indicating a high likelihood that human MERS-CoV in Saudi Arabia is unnatural in origin. The findings simply flag unusual patterns in this outbreak, but do not prove unnatural etiology. Proof of bioattacks can only be obtained by law enforcement and intelligence agencies. This study demonstrated the value and flexibility of the mGFT in assessing and predicting the risk for an ongoing outbreak with simple criteria.

Prevalence and predictors of influenza vaccination among residents of long-term care facilities.

Influenza is a respiratory illness which results in significant morbidity and mortality, especially in the older population. Older people living in Long-Term Care Facilities (LTCFs) have a significantly higher risk of infection and complications from influenza. Influenza vaccine is considered the best strategy to prevent infection in high-risk populations. In Australia, the Communicable Diseases Network Australia (CNDA) suggests a vaccination coverage rate of 95% in both staff and residents1. This study aims to measure the vaccination coverage rates for residents in LTCFs and identify predictors of vaccination uptake for these individuals. This study was conducted in nine LTCFs in four sites from March to September 2018. This was done via medical record reviews for residents over 65 years old in these LTCFs, collecting information such as vaccination status, age, gender, ethnicity and occupation. Simple and multivariable logistic regression was used to calculate the Odds Ratio (OR) to determine significant predictors of influenza vaccination uptake. The overall vaccination rate among LTCF residents was 83.6%. Significant predictors of vaccination were LTCF location, ethnicity and previous year vaccination status. Residents in LTCF Site D were less likely to be vaccinated compared to Site A (OR 0.11, 95% CI 0.02-0.61), non-Caucasians were less likely to get vaccinated (OR 0.09, 95% CI 0.01-0.67), and residents who refused the 2017 vaccine were less likely to be vaccinated (OR 0.04, 95% CI 0.01-0.15). Compared with previous Australian studies on LTCF vaccination rates, the overall vaccination rate was high in these LTCFs (83.6% versus 66-84%), but it varied across different sites. Reasons for varying vaccination rates should be explored further - for example, lower rates in non-Caucasians with diverse cultural backgrounds. Better understanding the causes of under-vaccination can help improve vaccination programs in LTCFs.

How Valid Are Assumptions About Re-emerging Smallpox? A Systematic Review of Parameters Used in Smallpox Mathematical Models.

Background: Globally eradicated in 1980, smallpox is listed as a category A bioterrorism agent. If smallpox were to re-emerge, it may be due to an act of bioterrorism or a laboratory accident, and the impact is likely to be severe. Preparedness against smallpox is subject to more uncertainty than other infectious diseases because it is eradicated, there is uncertainty about population immunity, and the current global health workforce has no practical experience or living memory of smallpox. In the event of re-emergence of smallpox, mathematical modeling plays a crucial role in improving the evidence base to inform preparedness, mitigation, and response activities. However, the predictions of mathematical models about outbreak magnitude and impact depend critically on the assumptions and disease parameters used. We aimed to identify modeling studies that would be applicable to re-emerging smallpox and to evaluate consistency and the certainty of the evidence published about the key parameters used. Methods: We conducted a systematic review using PRISMA criteria, of assumptions used in modeling studies on duration of latent, prodromal, and infectious period, as well as the choice of the basic reproduction number (R0) for re-emerging smallpox. We performed a literature search using PubMED, Scopus, Web of Science, and EMBASE and included peer-reviewed articles that focused on smallpox models, stated at least three of the aforementioned parameters and published in English. Findings: A total of 42 studies were selected for inclusion. There was general agreement on the duration of latent and prodromal periods, being 11-12 d (88%) and 3 d (59%), respectively. The duration of the infectious period varied from 4 to 20 d. Most models assumed 16 d (19%), 12 d (16.7%), and 8.6 d (12%) of infectiousness. In 25/34 studies, R0 ranged between 3 and 5, generally lower than the R0 calculated from past outbreaks. Discussion: Models of smallpox re-emergence also tend to use the same limited available historical data sources but assume a wide range of different estimates for key parameters. Models use very optimistic assumptions of decreased population immunity, despite high uncertainty about duration and magnitude of post-vaccination immunity. This review reveals a paradox. A substantial proportion of the modern population is unvaccinated, never exposed to boosting from wild-type smallpox, or immunocompromised; furthermore, vaccine-induced immunity wanes over time. Failure to consider these factors in a model will lead to underestimating the true impact of a re-emergent smallpox epidemic in the contemporary population.

Epidemiology of influenza B in Australia: 2001-2014 influenza seasons.

BACKGROUND: Influenza B is characterised by two antigenic lineages: B/Victoria and B/Yamagata. These lineages circulate together with influenza A during influenza seasons, with varying incidence from year to year and by geographic region. OBJECTIVE: To determine the epidemiology of influenza B relative to influenza A in Australia. METHODS: Laboratory-confirmed influenza notifications between 2001 and 2014 in Australia were obtained from the Australian National Notifiable Diseases Surveillance System. RESULTS: A total of 278 485 laboratory-confirmed influenza cases were notified during the study period, comprising influenza A (82.2%), B (17.1%) and 'other and untyped' (0.7%). The proportion of notifications that were influenza B was highest in five- to nine-year-olds (27.5%) and lowest in persons aged 85 years and over (11.5%). Of all B notifications with lineage determined, 77.1% were B/Victoria and 22.9% were B/Yamagata infections. Mismatches between the dominant B lineage in a season and the trivalent vaccine B lineage occurred in over one-third of seasons during the study years. In general, influenza B notifications peaked later than influenza A notifications. CONCLUSION: The proportion of circulating influenza B in Australia during 2001-2014 was slightly lower than the global average and was dominated by B/Victoria. Compared with influenza A, influenza B infection was more common among older children and young adults and less common in the very elderly. Influenza B lineage mismatch with the trivalent vaccine occurred about one-third of the time.

Phylogenetic analysis of human rhinoviruses collected over four successive years in Sydney, Australia.

BACKGROUND: Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza-like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere. OBJECTIVES: To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009. METHODS: Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Sequencing data of 5'UTR and VP4/VP2 coding regions on RT-PCR-positive specimens were analysed. RESULTS: Human rhinoviruses were detected by real-time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5'UTR and VP4/VP2 on HRV-positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5'UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032). CONCLUSION: Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships.

The Burden of Pertussis in Patients with and without Recurrent Ischaemic Vascular Events.

Pertussis seroepidemiology and associated factors in older adults aged ≥40 years with and without acute myocardial infarction (AMI) were studied to investigate whether unrecognised pertussis may precipitate AMI. Sera were obtained from a previous case-control study investigating the role of influenza in precipitating AMIs. Baseline sera were considered pertussis toxin (PT) IgG seropositive at levels ≥5 IU/mL. Levels ≥v62.5 IU/mL were considered indicative of infection in the previous year, and recent infection was indicative at levels ≥125 IU/mL. Of the serum samples tested, 55% (122/222) were seropositive for PT IgG, 5% (11/222) had evidence of infection in the past year and 1.4% (3/222) had evidence of recent infection. Evidence of infection in the past year was found in 3.2% of those aged 65-74 years. Overall, 47.8% of 40-64 year olds and 43.2% of those aged ≥65 years were seronegative for pertussis. Serological evidence of pertussis was not associated with AMI (46/92, 50.0% cases vs. 76/130, 58.5% controls, p=0.2). After adjusting for age, AMI and self-reported pertussis and GP verified influenza vaccination, females (OR = 2.2, 95% CI = 1.1-4.1, p=0.02) were more likely to be seronegative. Just under half of participants had no detectable pertussis immunity and are therefore susceptible to infection. Our study supports the need for an adult pertussis booster to supplement current recommendations.

Factors associated with the transmission of pandemic (H1N1) 2009 among hospital healthcare workers in Beijing, China.

BACKGROUND: With the increase in patient activity during the 2009 H1N1 pandemic, came an associated increase in occupational infections of healthcare workers (HCWs). OBJECTIVES: The aim of this study was to examine factors associated with the transmission of pandemic (H1N1) 2009 among HCWs. METHODS: A 1:4 matched case-control study by hospital, ward, age, and gender was conducted in HCWs from hospitals in Beijing during February 2010. Cases were diagnosed with pandemic (H1N1) 2009, and controls had neither influenza-like illness nor diagnosis with pandemic (H1N1) 2009 during August 2009 to January 2010. Information during 7 days before symptom onset of case was collected, and controls were queried about the same period. RESULTS: A total of 51 cases identified via National Notifiable Infectious Disease Surveillance System participated in this study. Controls were matched to cases for a total of 255 individuals. About 19·6% (10/51) of cases and 26·0% (53/204) of controls recalled they had conducted a high-risk procedure on a patient with pandemic (H1N1) 2009. 72·5% (37/51) of cases and 71·6% (146/204) of controls stated they wore medical masks in ≥80% of working time. Only 5·9% (3/51) and 36·3% (74/204) of cases and controls, respectively, reported receiving pandemic vaccination. Participants receiving pandemic vaccination had a significantly lower risk of infection during the pandemic (OR = 0·150, 95% CI: 0·047-0·479, P = 0·001). The estimated vaccine effectiveness was 85·0%. CONCLUSIONS: We showed a high vaccine effectiveness of the pandemic vaccine and that vaccination was the only factor significantly associated with risk of infection in HCWs.