Electronic Health Record-Based Algorithm for Monitoring Respiratory Virus-Like Illness.

Viral respiratory illness surveillance has traditionally focused on single pathogens (e.g., influenza) and required fever to identify influenza-like illness (ILI). We developed an automated system applying both laboratory test and syndrome criteria to electronic health records from 3 practice groups in Massachusetts, USA, to monitor trends in respiratory viral-like illness (RAVIOLI) across multiple pathogens. We identified RAVIOLI syndrome using diagnosis codes associated with respiratory viral testing or positive respiratory viral assays or fever. After retrospectively applying RAVIOLI criteria to electronic health records, we observed annual winter peaks during 2015-2019, predominantly caused by influenza, followed by cyclic peaks corresponding to SARS-CoV-2 surges during 2020-2024, spikes in RSV in mid-2021 and late 2022, and recrudescent influenza in late 2022 and 2023. RAVIOLI rates were higher and fluctuations more pronounced compared with traditional ILI surveillance. RAVIOLI broadens the scope, granularity, sensitivity, and specificity of respiratory viral illness surveillance compared with traditional ILI surveillance.

Virus matrix interference on assessment of virucidal activity of high-touch surfaces designed to prevent hospital-acquired infections.

OBJECTIVES/PURPOSE: High-touch surfaces are a critical reservoir in the spread of nosocomial infections. Although disinfection and infection control protocols are well developed, they lack the ability to passively reduce the pathogenic load of high-touch surfaces. Copper and its alloys have been suggested as a surface that exhibit continuous biocidal effects. Antimicrobial studies on these surfaces are prevalent, while virucidal studies are not as well explored. The goal of this study was to first determine the virucidal activity of a copper-nickel-zinc alloy and to then examine the effect of soiling and virus preparation on virucidal activity. METHODS: A baculovirus vector was used as an easily quantifiable model of an infectious enveloped animal cell virus. Droplets containing virus were deposited on surfaces and allowed to stay wet using humidity control or were dried onto the surface. Virus was then recovered from the surface and assayed for infectivity. To examine how the composition of the droplet affected the survival of the virus, 3 different soiling conditions were tested. The first two were recommended by the United States Environmental Protection Agency and the third consisted of cell debris resulting from virus amplification. RESULTS: A copper-nickel-zinc alloy was shown to have strong virucidal effects for an enveloped virus. Copper, nickel, and zinc ions were all shown to leach from the alloy surface and are the likely cause of virucidal activity by this surface. Virucidal activity was achieved under moderate soiling but lost under high soiling generated by routine virus amplification procedures. The surface was able to repeatably inactivate dried virus droplets under moderate soiling conditions, but unable to do so for virus droplets kept wet using high humidity. CONCLUSION: Ion leaching was associated with virucidal activity in both wet and dried virus conditions. Soiling protected the virus by quenching metal ions, and not by inhibiting leaching. The composition of the solution containing virus plays a critical role in evaluating the virucidal activity of surfaces and surface coatings.

An assessment of potential biomarkers of environment enteropathy and its association with age and microbial infections among children in Bangladesh.

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.

Quantitative Assessment of Viral Dispersion Associated with Respiratory Support Devices in a Simulated Critical Care Environment.

Rationale: Patients with severe coronavirus disease (COVID-19) require supplemental oxygen and ventilatory support. It is unclear whether some respiratory support devices may increase the dispersion of infectious bioaerosols and thereby place healthcare workers at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To quantitatively compare viral dispersion from invasive and noninvasive respiratory support modalities.Methods: This study used a simulated ICU room with a breathing-patient simulator exhaling nebulized bacteriophages from the lower respiratory tract with various respiratory support modalities: invasive ventilation (through an endotracheal tube with an inflated cuff connected to a mechanical ventilator), helmet ventilation with a positive end-expiratory pressure (PEEP) valve, noninvasive bilevel positive-pressure ventilation, nonrebreather face masks, high-flow nasal oxygen (HFNO), and nasal prongs.Measurements and Main Results: Invasive ventilation and helmet ventilation with a PEEP valve were associated with the lowest bacteriophage concentrations in the air, and HFNO and nasal prongs were associated with the highest concentrations. At the intubating position, bacteriophage concentrations associated with HFNO (2.66 × 104 plaque-forming units [PFU]/L of air sampled), nasal prongs (1.60 × 104 PFU/L of air sampled), nonrebreather face masks (7.87 × 102 PFU/L of air sampled), and bilevel positive airway pressure (1.91 × 102 PFU/L of air sampled) were significantly higher than those associated with invasive ventilation (P < 0.05 for each). The difference between bacteriophage concentrations associated with helmet ventilation with a PEEP valve (4.29 × 10-1 PFU/L of air sampled) and bacteriophage concentrations associated with invasive ventilation was not statistically significant.Conclusions: These findings highlight the potential differential risk of dispersing virus among respiratory support devices and the importance of appropriate infection prevention and control practices and personal protective equipment for healthcare workers when caring for patients with transmissible respiratory viral infections such as SARS-CoV-2.

Use of point-of-care molecular tests reduces hospitalization and oseltamivir administration in children presenting with influenza-like illness.

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point-of-care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza-like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0-16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision-making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01-9.82; p = .046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06-20.43; p = .041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs.

Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples.

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative.

Longitudinal monitoring of honey bee colonies reveals dynamic nature of virus abundance and indicates a negative impact of Lake Sinai virus 2 on colony health.

Honey bees (Apis mellifera) are important pollinators of plants, including those that produce nut, fruit, and vegetable crops. Therefore, high annual losses of managed honey bee colonies in the United States and many other countries threaten global agriculture. Honey bee colony deaths have been associated with multiple abiotic and biotic factors, including pathogens, but the impact of virus infections on honey bee colony population size and survival are not well understood. To further investigate seasonal patterns of pathogen presence and abundance and the impact of viruses on honey bee colony health, commercially managed colonies involved in the 2016 California almond pollination event were monitored for one year. At each sample date, colony health and pathogen burden were assessed. Data from this 50-colony cohort study illustrate the dynamic nature of honey bee colony health and the temporal patterns of virus infection. Black queen cell virus, deformed wing virus, sacbrood virus, and the Lake Sinai viruses were the most readily detected viruses in honey bee samples obtained throughout the year. Analyses of virus prevalence and abundance revealed pathogen-specific trends including the overall increase in deformed wing virus abundance from summer to fall, while the levels of Lake Sinai virus 2 (LSV2) decreased over the same time period. Though virus prevalence and abundance varied in individual colonies, analyses of the overall trends reveal correlation with sample date. Total virus abundance increased from November 2015 (post-honey harvest) to the end of the almond pollination event in March 2016, which coincides with spring increase in colony population size. Peak total virus abundance occurred in late fall (August and October 2016), which correlated with the time period when the majority of colonies died. Honey bee colonies with larger populations harbored less LSV2 than weaker colonies with smaller populations, suggesting an inverse relationship between colony health and LSV2 abundance. Together, data from this and other longitudinal studies at the colony level are forming a better understanding of the impact of viruses on honey bee colony losses.

Longitudinal profiling of the vaccination coverage in Brazil reveals a recent change in the patterns hallmarked by differential reduction across regions.

OBJECTIVE: Vaccination coverage is decreasing worldwide, favoring the potential reemergence of vaccine-preventable diseases. In this study, we performed a longitudinal characterization of vaccination coverage in Brazil and compared the profiles between the distinct regions in the country to test whether there has been a substantial change over the last 5 years. METHODS: De-identified publicly available data were retrieved from the repository of the Brazilian Ministry of Health, comprising detailed information on vaccination coverage in all age groups between 1994 and 2019. The vaccination coverage for the whole country and for each Brazilian region, by year, was examined, and a time-series pattern analysis was performed. RESULTS: A significant decrease in overall vaccination coverage across the country regions was observed between 2017 and 2019, especially in childhood immunization. A reduction in BCG, hepatitis B, influenza, and rotavirus vaccine coverage was observed. Conversely, vaccines against measles, mumps, rubella, varicella, and meningococcus showed an increase in coverage. Region-specific changes in vaccination patterns within the study period were observed. CONCLUSIONS: A substantial reduction in vaccination coverage was detected in Brazil, a country already highly susceptible to the emergence of epidemic infectious diseases. Continuing evaluation of the immunization program actions may help to improve vaccination coverage and prevent new epidemics.

Characterization of viral, bacterial, and parasitic causes of disease in small-scale chicken flocks in the Mekong Delta of Vietnam.

In the Mekong Delta region of Vietnam, small-scale chicken farming is common. However, high levels of disease or mortality in such flocks impair economic development and challenge the livelihoods of many rural households. We investigated 61 diseased small-scale flocks (122 chickens) for evidence of infection with 5 bacteria, 4 viruses, and helminths. Serological profiles (ELISA) were also determined against 6 of these pathogens. The aims of this study were the following: (1) to investigate the prevalence of different pathogens and to compare the probability of detection of bacterial pathogens using PCR and culture; (2) to investigate the relationship between detection of organisms in birds' tissues and the observed morbidity and mortality, as well as their antibody profile; and (3) to characterize risk factors for infection with specific viral or bacterial pathogens. We used PCR to test for viral (viruses causing infectious bronchitis [IB], highly pathogenic avian influenza [HPAI], Newcastle disease, and infectious bursal disease [IBD]) and bacterial pathogens (Mycoplasma gallisepticum, Pasteurella multocida, Avibacterium paragallinarum, and Ornithobacterium rhinotracheale [ORT]). The latter two were also investigated in respiratory tissues by conventional culture. Colisepticemic Escherichia coli was investigated by liver or spleen culture. In 49 of 61 (80.3%) flocks, at least one bacterial or viral pathogen was detected, and in 29 (47.5%) flocks, more than one pathogen was detected. A. paragallinarum was detected in 62.3% flocks, followed by M. gallisepticum (26.2%), viruses causing IBD (24.6%) and IB (21.3%), septicemic E. coli (14.8%), ORT (13.1%), and HPAI viruses (4.9%). Of all flocks, 67.2% flocks were colonized by helminths. Mortality was highest among flocks infected with HPAI (100%, interquartile range [IQR]: 81.6-100%) and lowest with flocks infected with ORT (5.3%, IQR: 1.1-9.0%). The results indicated slight agreement (kappa ≤ 0.167) between detection by PCR and culture for both A. paragallinarum and ORT, as well as between the presence of cestodes and ORT infection (kappa = 0.317). Control of A. paragallinarum, viruses causing HPAI, IBD, and IB, M. gallisepticum, and gastrointestinal helminths should be a priority in small-scale flocks.

Prioritization of livestock transboundary diseases in Belgium using a multicriteria decision analysis tool based on drivers of emergence.

During the past decade, livestock diseases have (re-)emerged in areas where they had been previously eradicated or never been recorded before. Drivers (i.e. factors of (re-)emergence) have been identified. Livestock diseases spread irrespective of borders, and therefore, reliable methods are required to help decision-makers to identify potential threats and try stopping their (re-)emergence. Ranking methods and multicriteria approaches are cost-effective tools for such purpose and were applied to prioritize a list of selected diseases (N = 29 including 6 zoonoses) based on the opinion of 62 experts in accordance with 50 drivers-related criteria. Diseases appearing in the upper ranking were porcine epidemic diarrhoea, foot-and-mouth disease, low pathogenic avian influenza, African horse sickness and highly pathogenic avian influenza. The tool proposed uses a multicriteria decision analysis approach to prioritize pathogens according to drivers and can be applied to other countries or diseases.

Virology Tests in Brain-Dead Donors: Let the Bills Run Up?

OBJECTIVES: In the organ donation process, screening for serologic markers for a selection of agents is essential to prevent infection transmission. The screening of donors for specific potential infections can never absolutely exclude the risk of transmission. For reevaluation of serology tests, we analyzed results of tests requested for all brain-dead donors. MATERIALS AND METHODS: Our study included all actual brain-dead donors who were seen from January 2017 to February 2018, received ancillary tests, and had final confirmation of brain death at our organ procurement unit. RESULTS: Most candidates for organ and tissue donation were seronegative for intended agents. We found that 14.4% of the samples were suspicious for infectious and needed further evaluation; 12.2% of donors had positive results corresponding to hepatitis B, and only 1.9% were rejected from donation. Requisiteness to DNA detection for hepatitis B virus infection was mainly related to age over 50 years. CONCLUSIONS: The process of donor screening must systemically assess the donor. At the final stage, essential biomarkers must be investigated. Application of more caution in evaluation of older donors, including more screening tests before transfer to the operating room, remains mandatory.

Impact of infection on risk of Parkinson's disease: a quantitative assessment of case-control and cohort studies.

Identifying modifiable risk factors for Parkinson's disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07-1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32-1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.

The effect of delay in viral production in within-host models during early infection.

Delay in viral production may have a significant impact on the early stages of infection. During the eclipse phase, the time from viral entry until active production of viral particles, no viruses are produced. This delay affects the probability that a viral infection becomes established and timing of the peak viral load. Deterministic and stochastic models are formulated with either multiple latent stages or a fixed delay for the eclipse phase. The deterministic model with multiple latent stages approaches in the limit the model with a fixed delay as the number of stages approaches infinity. The deterministic model framework is used to formulate continuous-time Markov chain and stochastic differential equation models. The probability of a minor infection with rapid viral clearance as opposed to a major full-blown infection with a high viral load is estimated from a branching process approximation of the Markov chain model and the results are confirmed through numerical simulations. In addition, parameter values for influenza A are used to numerically estimate the time to peak viral infection and peak viral load for the deterministic and stochastic models. Although the average length of the eclipse phase is the same in each of the models, as the number of latent stages increases, the numerical results show that the time to viral peak and the peak viral load increase.

HEALTH ASSESSMENT OF FREE-RANGING CHELONIANS IN AN URBAN SECTION OF THE BRONX RIVER, NEW YORK, USA.

The Bronx River in Bronx, New York, US spans an area of significant human development and has been subject to historic and ongoing industrial contamination. We evaluated the health of freeranging native common snapping turtles ( Chelydra serpentina) and nonnative invasive red-eared sliders ( Trachemys scripta) in a segment of the Bronx River between May and July 2012. In 18 snapping turtles and nine sliders, complete physical examinations were performed, ectoparasites collected, and blood was analyzed for contaminants (mercury, thallium, cadmium, arsenic, lead, selenium, oxychlordane, alpha-chlordane, dieldrin, DDD, DDE, polychlorinated biphenyls). Complete blood counts and the presence of hemoparasites were determined in 16 snapping turtles and nine sliders. Swabs of the choana and cloaca were screened for ranavirus, adenovirus, herpesvirus, and Mycoplasma spp. by PCR in 39 snapping turtles and 28 sliders. Both turtle species exhibited bioaccumulation of various environmental contaminants, particularly organochlorines and polychlorinated biphenyls. Molecular screening revealed a unique herpesvirus in each species. A Mycoplasma sp. previously isolated from emydid turtles was detected in red-eared sliders while a unique Mycoplasma sp. was identified in common snapping turtles. Ranaviruses and adenoviruses were not detected. Our study established a baseline health assessment to which future data can be compared. Moreover, it served to expand the knowledge and patterns of health markers, environmental contaminants, and microorganisms of freeranging chelonians.

Global trends in infectious diseases of swine.

Pork accounts for more than one-third of meat produced worldwide and is an important component of global food security, agricultural economies, and trade. Infectious diseases are among the primary constraints to swine production, and the globalization of the swine industry has contributed to the emergence and spread of pathogens. Despite the importance of infectious diseases to animal health and the stability and productivity of the global swine industry, pathogens of swine have never been reviewed at a global scale. Here, we build a holistic global picture of research on swine pathogens to enhance preparedness and understand patterns of emergence and spread. By conducting a scoping review of more than 57,000 publications across 50 years, we identify priority pathogens globally and regionally, and characterize geographic and temporal trends in research priorities. Of the 40 identified pathogens, publication rates for eight pathogens increased faster than overall trends, suggesting that these pathogens may be emerging or constitute an increasing threat. We also compared regional patterns of pathogen prioritization in the context of policy differences, history of outbreaks, and differing swine health challenges faced in regions where swine production has become more industrialized. We documented a general increasing trend in importance of zoonotic pathogens and show that structural changes in the industry related to intensive swine production shift pathogen prioritization. Multinational collaboration networks were strongly shaped by region, colonial ties, and pig trade networks. This review represents the most comprehensive overview of research on swine infectious diseases to date.

The role of spatial heterogeneity in the evolution of local and global infections of viruses.

Viruses have two modes spread in a host body, one is to release infectious particles from infected cells (global infection) and the other is to infect directly from an infected cell to an adjacent cell (local infection). Since the mode of spread affects the evolution of life history traits, such as virulence, it is important to reveal what level of global and local infection is selected. Previous studies of the evolution of global and local infection have paid little attention to its dependency on the measures of spatial configuration. Here we show the evolutionarily stable proportion of global and local infection, and how it depends on the distribution of target cells. Using an epidemic model on a regular lattice, we consider the infection dynamics by pair approximation and check the evolutionarily stable strategy. We also conduct the Monte-Carlo simulation to observe evolutionary dynamics. We show that a higher local infection is selected as target cells become clustered. Surprisingly, the selected strategy depends not only on the degree of clustering but also the abundance of target cells per se.

Multiplex Respiratory Virus Testing for Antimicrobial Stewardship: A Prospective Assessment of Antimicrobial Use and Clinical Outcomes Among Hospitalized Adults.

Background: Respiratory tract infections are frequent causes of hospitalization and initiation of empirical antimicrobial therapy. Testing for a broad panel of respiratory viruses has been advocated as a useful tool for antibiotic stewardship. We conducted a prospective observational study to assess the impact of rapid viral test results on antimicrobial prescriptions and clinical outcomes among hospitalized adults. Methods: Eight hundred patients admitted with respiratory symptoms were tested by a 12-virus respiratory panel (RVP) during 3 consecutive winters in Montreal, Canada. The primary outcome measure was change in antimicrobial prescriptions (ie, de-escalation of empirical antimicrobial therapy or commencement of new antimicrobial therapy) after RVP results were available. Clinical outcomes were also assessed. Results: Influenza virus was identified in 53% of individuals in the study population, and other viruses were identified in 10%. Influenza virus positivity was associated with shorter duration of hospitalization and appropriate antiviral management. Antibiotic management was most significantly correlated with radiographic suspicion of pneumonia and less so with results of the RVP. Positivity for viruses other than influenza virus was not correlated with significantly different outcomes. Conclusions: Physicians respond to results of testing for influenza virus when managing hospitalized adult patients but respond less to test results for other viruses. These data can inform the design of stewardship interventions and the selection of viral testing panels for hospitalized patients.

Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management.

Organ and stem cell transplantation has been one of the greatest advances in modern medicine, and is the primary treatment modality for many end-stage diseases. As our population ages, so do the transplant recipients, and with that comes many new challenges. Respiratory viruses have been a large contributor to the mortality and morbidity of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Respiratory viruses are generally a long-term complication of transplantation and primarily acquired in the community. With the emergence of molecular methods, newer respiratory viruses are being detected. Respiratory viruses appear to cause severe disease in the older transplant population. Influenza vaccine remains the mainstay of prevention in transplant recipients, although immunogenicity of current vaccines is suboptimal. Limited therapies are available for other respiratory viruses. The next decade will likely bring newer antivirals and vaccines to the forefront. Our goal is to provide the most up to date knowledge of respiratory viral infections in our aging transplant population.