The association between influenza vaccine effectiveness and egg-based manufacturing technology: literature review and US expert consensus.

BACKGROUND: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. METHODS: This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). RESULTS: Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52-86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. CONCLUSION: After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE.

Strategies to prevent surgical site infections in acute-care hospitals: 2022 Update.

The intent of this document is to highlight practical recommendations in a concise format designed to assist acute-care hospitals in implementing and prioritizing their surgical-site infection (SSI) prevention efforts. This document updates the Strategies to Prevent Surgical Site Infections in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Preschool-Aged Household Contacts as a Risk Factor for Viral Respiratory Infections in Healthcare Personnel.

Background: Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings. Methods: We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011-2012 to 2014-2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0-5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction-detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level. Results: Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05-1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09-1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts. Conclusions: Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings.

Protecting Pediatric Healthcare Personnel With Personal Protective Equipment-Specific Roles.

During the height of the COVID-19 pandemic, organizations had to prioritize protecting healthcare personnel (HCP) through effective communication and providing necessary personal protective equipment (PPE). Inadequate and inconsistent supply of PPE has been noted as a cause of anxiety and concern for HCPs. A pediatric hospital in the Western United States responded by developing a system of processes to protect their staff. This column describes the creation of specific COVID-19 roles to support the communication and the resourcing of PPE.

Influence of Preseason Antibodies Against Influenza Virus on Risk of Influenza Infection Among Healthcare Personnel.

BACKGROUND: The association of hemagglutination inhibition (HAI) antibodies with protection from influenza among healthcare personnel (HCP) with occupational exposure to influenza viruses has not been well-described. METHODS: The Respiratory Protection Effectiveness Clinical Trial was a cluster-randomized, multisite study that compared medical masks to N95 respirators in preventing viral respiratory infections among HCP in outpatient healthcare settings for 5180 participant-seasons. Serum HAI antibody titers before each influenza season and influenza virus infection confirmed by polymerase chain reaction were studied over 4 study years. RESULTS: In univariate models, the risk of influenza A(H3N2) and B virus infections was associated with HAI titers to each virus, study year, and site. HAI titers were strongly associated with vaccination. Within multivariate models, each log base 2 increase in titer was associated with 15%, 26% and 33%-35% reductions in the hazard of influenza A(H3N2), A(H1N1), and B infections, respectively. Best models included preseason antibody titers and study year, but not other variables. CONCLUSIONS: HAI titers were associated with protection from influenza among HCP with routine exposure to patients with respiratory illness and influenza season contributed to risk. HCP can be reassured about receiving influenza vaccination to stimulate immunity.

Impact of mandatory vaccination of healthcare personnel on rates of influenza and other viral respiratory pathogens.

OBJECTIVE: The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings. SETTING: Four Veterans' Affairs (VA) health systems and three non-VA medical centers. METHODS: We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies. RESULTS: Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13-0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02-1.57). CONCLUSIONS: Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%-53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.

Outpatient healthcare personnel knowledge and attitudes towards infection prevention measures for protection from respiratory infections.

BACKGROUND: Healthcare personnel (HCP) knowledge and attitudes toward infection control measures are important determinants of practices that can protect them from transmission of infectious diseases. METHODS: Healthcare personnel were recruited from Emergency Departments and outpatient clinics at seven sites. They completed knowledge surveys at the beginning and attitude surveys at the beginning and end of each season of participation. Attitudes toward infection prevention and control measures, especially medical masks and N95 respirators, were compared. The proportion of participants who correctly identified all components of an infection control bundle for seven clinical scenarios was calculated. RESULTS: The proportion of participants in the medical mask group who reported at least one reason to avoid using medical masks fell from 88.5% on the pre-season survey to 39.6% on the post-season survey (odds ratio [OR] for preseason vs. postseason 0.11, 95% CI 0.10-0.14). Among those wearing N95 respirators, the proportion fell from 87.9% to 53.6% (OR 0.24, 95% CI 0.21-0.28). Participants correctly identified all components of the infection control bundle for 4.9% to 38.5% of scenarios. CONCLUSIONS: Attitudes toward medical masks and N95 respirators improved significantly between the beginning and end of each season. The proportion of HCP who correctly identified the infection control precautions needed for clinical scenarios was low, but it improved over successive years of participation in the study.

Take-home kits to detect respiratory viruses among healthcare personnel: Lessons learned from a cluster randomized clinical trial.

BACKGROUND: Health care personnel (HCP) working in outpatient settings routinely interact with patients with acute respiratory illnesses. Absenteeism following symptom development and lack of staff trained to obtain samples limit efforts to identify pathogens among infected HCP. METHODS: The Respiratory Protection Effectiveness Clinical Trial assessed respiratory infection incidence among HCP between 2011 and 2015. Research assistants obtained anterior nasal and oropharyngeal swabs from HCP in the workplace following development of respiratory illness symptoms and randomly while asymptomatic. Participants received take-home kits to self-collect swabs when absent from work. Samples mailed to a central laboratory were tested for respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: Among 2,862 participants, 3,467 swabs were obtained from symptomatic participants. Among symptomatic HCP, respiratory virus was detected in 904 of 3,467 (26.1%) samples. Self-collected samples by symptomatic HCP at home had higher rates of viral detection (40.3%) compared to 24% obtained by trained research assistants in the workplace (P < .001). CONCLUSIONS: In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.

Risk Factors for Healthcare Personnel Infection With Endemic Coronaviruses (HKU1, OC43, NL63, 229E): Results from the Respiratory Protection Effectiveness Clinical Trial (ResPECT).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a large risk to healthcare personnel (HCP). Quantifying the risk of coronavirus infection associated with workplace activities is an urgent need. METHODS: We assessed the association of worker characteristics, occupational roles and behaviors, and participation in procedures with the risk of endemic coronavirus infection among HCP who participated in the Respiratory Protection Effectiveness Clinical Trial (ResPECT), a cluster randomized trial to assess personal protective equipment to prevent respiratory infections and illness conducted from 2011 to 2016. RESULTS: Among 4689 HCP seasons, we detected coronavirus infection in 387 (8%). HCP who participated in an aerosol-generating procedure (AGP) at least once during the viral respiratory season were 105% (95% confidence interval, 21%-240%) more likely to be diagnosed with a laboratory-confirmed coronavirus infection. Younger individuals, those who saw pediatric patients, and those with household members <5 years of age were at increased risk of coronavirus infection. CONCLUSIONS: Our analysis suggests that the risk of HCP becoming infected with an endemic coronavirus increases approximately 2-fold with exposures to AGPs. Our findings may be relevant to the coronavirus disease 2019 (COVID-19) pandemic; however, SARS-CoV-2, the virus that causes COVID-19, may differ from endemic coronaviruses in important ways. CLINICAL TRIALS REGISTRATION: NCT01249625.

Chemical-Biological Terrorism and Its Impact on Children.

Children are potential victims of chemical or biological terrorism. In recent years, children have been victims of terrorist acts such as the chemical attacks (2017-2018) in Syria. Consequently, it is necessary to prepare for and respond to the needs of children after a chemical or biological attack. A broad range of public health initiatives have occurred since the terrorist attacks of September 11, 2001. However, in many cases, these initiatives have not ensured the protection of children. Since 2001, public health preparedness has broadened to an all-hazards approach, in which response plans for terrorism are blended with those for unintentional disasters or outbreaks (eg, natural events such as earthquakes or pandemic influenza or man-made catastrophes such as a hazardous-materials spill). In response to new principles and programs that have evolved over the last decade, this technical report supports the accompanying update of the American Academy of Pediatrics 2006 policy statement "Chemical-Biological Terrorism and its Impact on Children." The roles of the pediatrician and public health agencies continue to evolve, and only their coordinated readiness and response efforts will ensure that the medical and mental health needs of children will be met successfully. In this document, we will address chemical and biological incidents. Radiation disasters are addressed separately.

Chemical-Biological Terrorism and Its Impact on Children.

Chemical and biological events (including infectious disease outbreaks) may affect children disproportionately, and the threat of a chemical or biological attack remains in the United States and worldwide. Although federal programs and funding support a broad range of federal initiatives for public health preparedness and response, funding at the state and local levels has been flat or is decreasing, potentially leaving communities vulnerable. Consequently, pediatricians need to prepare and be ready to care for children in their communities before, during, and after a chemical or biological event, including during long-term recovery. Some medical countermeasures for particular chemical and biological agents have not been adequately studied or approved for children. The American Academy of Pediatrics provides resources and education on disaster preparedness and response, including information on the pediatrician's role in disasters, pediatric medical countermeasures, and mental health after an event as well as individual and family preparedness. This policy statement addresses the steps that clinicians and policy makers can take to protect children and mitigate the effects of a chemical or biological attack.

Evaluating the ALERT algorithm for local outbreak onset detection in seasonal infectious disease surveillance data.

Estimation of epidemic onset timing is an important component of controlling the spread of seasonal infectious diseases within community healthcare sites. The Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm uses a threshold-based approach to suggest incidence levels that historically have indicated the transition from endemic to epidemic activity. In this paper, we present the first detailed overview of the computational approach underlying the algorithm. In the motivating example section, we evaluate the performance of ALERT in determining the onset of increased respiratory virus incidence using laboratory testing data from the Children's Hospital of Colorado. At a threshold of 10 cases per week, ALERT-selected intervention periods performed better than the observed hospital site periods (2004/2005-2012/2013) and a CUSUM method. Additional simulation studies show how data properties may effect ALERT performance on novel data. We found that the conditions under which ALERT showed ideal performance generally included high seasonality and low off-season incidence.

N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial.

Importance: Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections. Objective: To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP. Design, Setting, and Participants: A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups. Interventions: Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness. Main Outcomes and Measures: The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed. Results: Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group. Conclusions and Relevance: Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza. Trial Registration: ClinicalTrials.gov Identifier: NCT01249625.

Protecting Healthcare Personnel in Outpatient Settings: The Influence of Mandatory Versus Nonmandatory Influenza Vaccination Policies on Workplace Absenteeism During Multiple Respiratory Virus Seasons.

OBJECTIVE To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP). DESIGN Retrospective observational cohort study. SETTING This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies. PARTICIPANTS The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites. METHODS To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012-2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models. RESULTS The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07-0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012-2013 and 2013-2014, 0.82; 95% CI, 0.72-0.93; OR for 2014-2015, 0.81; 95% CI, 0.69-0.95). CONCLUSIONS These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies. Infect Control Hosp Epidemiol 2018;39:452-461.

Which Comorbid Conditions Should We Be Analyzing as Risk Factors for Healthcare-Associated Infections?

OBJECTIVE To determine which comorbid conditions are considered causally related to central-line associated bloodstream infection (CLABSI) and surgical-site infection (SSI) based on expert consensus. DESIGN Using the Delphi method, we administered an iterative, 2-round survey to 9 infectious disease and infection control experts from the United States. METHODS Based on our selection of components from the Charlson and Elixhauser comorbidity indices, 35 different comorbid conditions were rated from 1 (not at all related) to 5 (strongly related) by each expert separately for CLABSI and SSI, based on perceived relatedness to the outcome. To assign expert consensus on causal relatedness for each comorbid condition, all 3 of the following criteria had to be met at the end of the second round: (1) a majority (>50%) of experts rating the condition at 3 (somewhat related) or higher, (2) interquartile range (IQR)≤1, and (3) standard deviation (SD)≤1. RESULTS From round 1 to round 2, the IQR and SD, respectively, decreased for ratings of 21 of 35 (60%) and 33 of 35 (94%) comorbid conditions for CLABSI, and for 17 of 35 (49%) and 32 of 35 (91%) comorbid conditions for SSI, suggesting improvement in consensus among this group of experts. At the end of round 2, 13 of 35 (37%) and 17 of 35 (49%) comorbid conditions were perceived as causally related to CLABSI and SSI, respectively. CONCLUSIONS Our results have produced a list of comorbid conditions that should be analyzed as risk factors for and further explored for risk adjustment of CLABSI and SSI. Infect Control Hosp Epidemiol 2017;38:449-454.

The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.

BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).

Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation.

BACKGROUND: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. METHODS: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ(2) tests were used to test for statistical significance. FINDINGS: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039). INTERPRETATION: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. FUNDING: None.