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.

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.

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.

An open challenge to advance probabilistic forecasting for dengue epidemics.

A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project-integration with public health needs, a common forecasting framework, shared and standardized data, and open participation-can help advance infectious disease forecasting beyond dengue.

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.

Guanine-based structural coloration as an indicator of oxidative stress in a cichlid fish.

Vertebrate pigmentation is known to be influenced by oxidative stress, but few studies have tested the hypothesis that structural coloration can be similarly affected. We tested whether fish iridophores, which produce structural color using guanine stacks, might be affected by the prooxidant-antioxidant balance of the animal. Specifically, we hypothesized that convict cichlids (Amatitlania nigrofasciata) metabolize guanine present in iridophores to uric acid, an antioxidant, in response to oxidative damage. We used Hunter's contrast gloss and high performance liquid chromatography to determine whether dietary guanine supplementation allows fish to maintain their structural coloration despite oxidative stress induced via ultraviolet-B (UV-B) radiation. We found that dietary guanine was associated with greater skin gloss, and that exposure to UV-B light reduced glossiness. UV-B exposure did not increase oxidative damage (acrolein) or total antioxidant capacity in the skin or liver. Our experiment did not detect effects of dietary guanine or UV-B light on uric acid, but uric acid was positively related to antioxidant capacity. Our results support the hypothesis that structural color in fish may be altered by environmental stressors such as exposure to UV light, and highlight the need for future studies to consider the role of iridophores in condition-dependent visual signaling.

Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake.

Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I), apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH). The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4-6 days post-fertilization (dpf). Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish apolipoproteins and serves as a springboard for future investigations to elucidate their roles in development and disease in the larval zebrafish model.

Dietary carotenoids do not improve motility or antioxidant capacity in cichlid fish sperm.

Carotenoids may act as antioxidants under many circumstances. We examined the importance of carotenoids as antioxidants in the gonads of male convict cichlids (Amatitlania nigrofasciata), a species in which males lack the carotenoid-based breeding coloration that characterizes females. Male fish were fed one of four diets that included different combinations of xanthophyll and carotene carotenoids, and then we measured carotenoid concentration of the gonads, gonadosomatic index (GSI), sperm motility, and the antioxidant capacity of the gonads. Significant differences were found in gonadal carotenoid content among treatment groups, suggesting that dietary carotenoids were indeed sequestered in the gonads. There were no differences among diet groups, however, in GSI, sperm motility, or gonadal antioxidant capacity. These findings suggest that carotenoids are required only in small amounts in the testes of male convict cichlids or that they play a limited role in protecting sperm from oxidative damage.

Carotenoid-based coloration in cichlid fishes.

Animal colors play important roles in communication, ecological interactions and speciation. Carotenoid pigments are responsible for many yellow, orange and red hues in animals. Whereas extensive knowledge on the proximate mechanisms underlying carotenoid coloration in birds has led to testable hypotheses on avian color evolution and signaling, much less is known about the expression of carotenoid coloration in fishes. Here, we promote cichlid fishes (Perciformes: Cichlidae) as a system in which to study the physiological and evolutionary significance of carotenoids. Cichlids include some of the best examples of adaptive radiation and color pattern diversification in vertebrates. In this paper, we examine fitness correlates of carotenoid pigmentation in cichlids and review hypotheses regarding the signal content of carotenoid-based ornaments. Carotenoid-based coloration is influenced by diet and body condition and is positively related to mating success and social dominance. Gaps in our knowledge are discussed in the last part of this review, particularly in the understanding of carotenoid metabolism pathways and the genetics of carotenoid coloration. We suggest that carotenoid metabolism and transport are important proximate mechanisms responsible for individual and population-differences in cichlid coloration that may ultimately contribute to diversification and speciation.

Exposure to 17α-ethinylestradiol decreases motility and ATP in sperm of male fighting fish Betta splendens.

The synthetic estrogen 17α-ethinylestradiol (EE2) is an endocrine-disrupting chemical released into aquatic environments from sewage treatment facilities. We tested the effects of two environmentally relevant concentrations of waterborne EE2, 10 and 100 ng L(-1) , on reproductive endpoints in the teleost fish Betta splendens. In the first experiment, testes were removed from males and sperm were exposed to EE2 directly through the activation water. Direct exposure to EE2 had no effect on any measure of sperm swimming performance. In the second experiment, we exposed sexually mature male B. splendens to EE2 using a semi-static exposure protocol for 4 weeks. There were no significant treatment effects in the 10 ng L(-1) treatment group, but at the 100 ng L(-1) dose we found that fish had smaller gonads and reduced sperm swimming velocity. When allowed to interact freely with female conspecifics, males exposed to 100 ng L(-1) EE2 built smaller nests and showed a nonsignificant decrease in fertilization success. To investigate further the potential mechanism underlying the decrease in sperm quality, we repeated the chronic exposure experiment and analyzed the ATP content of sperm from fish in each treatment group. We found that males exposed to 100 ng L(-1) of EE2 had fewer moles of ATP per sperm than did fish in the other two treatment groups, suggesting that a decrease in intracellular ATP caused a reduction in sperm swimming velocity. The current study adds to the growing body of literature that indicates the risks to aquatic organisms of exposure to environmentally relevant concentrations of EE2.

Dietary carotenoids increase yellow nonpigment coloration of female convict cichlids (Amantitlania nigrofasciata).

The carotenoid trade-off hypothesis states that diet-derived carotenoids are traded off among competing physiological demands, but this statement is rarely tested in ornamented females. In this study, reverse sexually dimorphic convict cichlids (Amantitlania nigrofasciata) were fed diets containing carotenoid supplementation at three biologically relevant levels for 12 wk. This treatment was followed by spectral, microscopic, and chemical analysis to determine how females allocated the pigments to tissues and how those decisions affected their ventral patch coloration. Yellow coloration of the integument increased with carotenoids in the diet, as did carotenoids deposited in ovaries, but diet did not change carotenoid allocation to skin. The results of this study suggest that females have the ability to modulate their expression of yellow coloration via an alternative coloration strategy. Gonadosomatic index and tank environment were also related to ventral patch color, supporting previous behavioral work highlighting the importance of social selection in reinforcing signal honesty.

Fighting fish (Betta splendens) bubble nests do not inhibit microbial growth.

Some organisms produce antimicrobial substances in nesting foam to favorably manipulate the environment to which their developing offspring are exposed. We tested if fighting fish Betta splendens foamy nest material, which is comprised of bubbles produced in the oral cavity of nesting males, has antimicrobial properties against a pathogenic bacteria (Edwardsiella tarda), a nonpathogenic bacteria (Escherichia coli), or a pathogenic oomycete (Saprolegnia parasitica). We also tested if exposure to nest material increases larval survival by performing in vitro fertilizations and individually incubating eggs in bubble nest extract or tank water (control). Our results show no evidence of antimicrobial properties of bubble nests. On the contrary, bubble nests provided favorable microenvironments for the growth of Saprolegnia parasitica. Our results confirm earlier work citing the importance of male nest attendance, and suggest that the mechanism responsible for decreased survival in the absence of attending males is pathogenic microbes.

Reproductive consequences of exposure to waterborne phytoestrogens in male fighting fish Betta splendens.

Phytoestrogens are plant compounds that can act as endocrine disruptors in vertebrates. Biologically active levels of phytoestrogens have been found in aquatic habitats near wood pulp and paper mills, biofuel manufacturing plants, sewage-treatment plants, and agricultural fields. Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success. In one experiment, we exposed sexually mature male fighting fish Betta splendens to environmentally relevant (1 µg L(-1)) and pharmacological concentrations (1000 µg L(-1)) of the phytoestrogen genistein as well as to a positive control of waterborne 17ß-estradiol (E2; 1 µg L(-1)), and a negative control of untreated water. In a second experiment, we exposed male B. splendens to environmentally relevant concentrations (1 µg L(-1)) of genistein and ß-sitosterol singly and in combination as well as to the positive and negative controls. All exposures were 21 days in duration. We measured sex-steroid hormone levels, gonadosomatic index (GSI), sperm concentration and motility, and fertilization success in these fish. We found that exposure to genistein did not affect circulating levels of the androgen 11-ketotestosterone or the estrogen E2 relative to negative-control fish. We also found that neither of the compounds nor their mixture affected GSI, sperm concentration or motility, or fertilization success in exposed fish relative to negative-control fish. However, fish exposed to phytoestrogens showed some evidence of fewer but more motile sperm than fish exposed to the positive control E2. We conclude that sexually mature male B. splendens are relatively immune to reproductive impairments from short-term exposure to waterborne phytoestrogens.

Testing the carotenoid trade-off hypothesis in the polychromatic Midas cichlid, Amphilophus citrinellus.

Many animals use carotenoid pigments derived from their diet for coloration and immunity. The carotenoid trade-off hypothesis predicts that, under conditions of carotenoid scarcity, individuals may be forced to allocate limited carotenoids to either coloration or immunity. In polychromatic species, the pattern of allocation may differ among individuals. We tested the carotenoid trade-off hypothesis in the Midas cichlid, Amphilophus citrinellus, a species with two ontogenetic color morphs, barred and gold, the latter of which is the result of carotenoid expression. We performed a diet-supplementation experiment in which cichlids of both color morphs were assigned to one of two diet treatments that differed only in carotenoid content (beta-carotene, lutein, and zeaxanthin). We measured integument color using spectrometry, quantified carotenoid concentrations in tissue and plasma, and assessed innate immunity using lysozyme activity and alternative complement pathway assays. In both color morphs, dietary carotenoid supplementation elevated plasma carotenoid circulation but failed to affect skin coloration. Consistent with observable differences in integument coloration, we found that gold fish sequestered more carotenoids in skin tissue than barred fish, but barred fish had higher concentrations of carotenoids in plasma than gold fish. Neither measure of innate immunity differed between gold and barred fish, or as a function of dietary carotenoid supplementation. Lysozyme activity, but not complement activity, was strongly affected by body condition. Our data show that a diet low in carotenoids is sufficient to maintain both coloration and innate immunity in Midas cichlids. Our data also suggest that the developmental transition from the barred to gold morph is not accompanied by a decrease in innate immunity in this species.