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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. [ABSTRACT FROM AUTHOR]

The recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp 120HIV vaccine is described. The men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial.

• MAS-1 adjuvant with 9 µg per hemagglutinin in 0.3 mL was safe and immunogenic in the elderly. • Antibodies to adjuvanted vaccine peaked by 85 days and were durable at 169 days. • Responses to adjuvanted vaccine appeared better than high dose influenza vaccine. • Adjuvanted vaccine induced seroresponses to non-study vaccine strains. • Late injection site reactions occurred with adjuvanted vaccine 0.5 mL dose volume. Increased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. A phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers. Forty-five subjects, aged 65–83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses. MAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• MAS-1 water-in-oil adjuvant with reduced doses of hemagglutinin (HA) was evaluated. • HA + MAS-1 was safe and more immunogenic than standard dose unadjuvanted vaccine. • Antibody responses were maintained up to 6 months with adjuvanted vaccine. • Antibodies to some non-study vaccine strains were higher in adjuvanted vaccine groups. • MAS-1 adjuvant offered HA dose-sparing effects and durable immunity in young adults. New influenza vaccines are needed to increase vaccine efficacy. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational low viscosity, free-flowing, water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. A phase 1, double-blind, safety and immunogenicity, HA dose escalation, randomized clinical trial was conducted. MAS-1 adjuvant with 1, 3, 5 or 9 µg per HA derived from licensed seasonal trivalent high dose inactivated influenza vaccine (IIV, Fluzone HD 60 µg per HA) in a 0.3 mL dose were compared to standard dose IIV (Fluzone SD, 15 µg per HA). Safety was measured by reactogenicity, adverse events, and clinical laboratory tests. Serum hemagglutination inhibition (HAI) antibody titers were measured for immunogenicity. Seventy-two subjects, aged 18–47 years, received one dose of either 0.3 mL adjuvanted vaccine or SD IIV intramuscularly. Common injection site and systemic reactions post-vaccination were mild tenderness, induration, pain, headache, myalgia, malaise and fatigue. All reactions resolved within 14 days post-vaccination. Safety laboratory measures were not different between groups. Geometric mean antibody titers, geometric mean fold increases in antibody titer, seroconversion rates and seroprotection rates against vaccine strains were in general higher and of longer duration (day 85 and 169 visits) with MAS-1-adjuvanted IIV at all doses of HA compared with SD IIV. Adjuvanted vaccine induced higher antibody responses against a limited number of non-study vaccine influenza B and A/H3N2 viruses including ones from subsequent years. MAS-1 adjuvant in a 0.3 mL dose volume provided HA dose-sparing effects without safety concerns and induced higher HAI antibody and seroconversion responses through at least 6 months, demonstrating potential to provide greater vaccine efficacy throughout an influenza season in younger adults. In summary, MAS-1 may provide enhanced, more durable and broader protective immunity compared with non-adjuvanted SD IIV. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Healthcare personnel knowledge of infection prevention measures is suboptimal • Baseline attitudes toward medical masks and N95 respirators were negative. • Participants' attitudes improved significantly during each respiratory virus season • Improved infection control education in the outpatient setting is needed Healthcare personnel (HCP) knowledge and attitudes toward infection control measures are important determinants of practices that can protect them from transmission of infectious diseases. 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. 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. 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. [ABSTRACT FROM AUTHOR]

• Health care personnel routinely exposed to respiratory viruses in the workplace. • Infectious disease outbreaks require timely and wide availability of diagnostics. • Take-home kits are a reasonable alternative to swabs obtained by trained workers. • Respiratory virus yields from take-home kits were satisfactory. • Take-home kit self-collection can diminish workplace exposure and PPE demand. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme‐linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV‐associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21‐40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections. Highlights: Antibodies to common coronaviruses (HCoV) were higher in older than younger adults.Antibodies to HCoV can be cross‐reactive between strains.More HCoV‐related respiratory illnesses were detected in younger than older adults, and binding antibodies to HCoV increased with respiratory illness more frequently than neutralizing antibodies.There were correlations between binding and neutralizing antibodies, especially to related HCoV strains in convalescent sera.Pre‐existing antibodies to HCoV may not necessarily be protective against repeated infections and lower rates of neutralizing antibody stimulation may contribute to susceptibility to re‐infection.Assessment of binding antibodies to HCoV may be useful in seroepidemiologic studies of HCoV infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]