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Applied and Environmental Microbiology Sep 2018Nosocomial viral infections are an important cause of health care-acquired infections where fomites have a role in transmission. Using stochastic modeling to quantify...
Nosocomial viral infections are an important cause of health care-acquired infections where fomites have a role in transmission. Using stochastic modeling to quantify the effects of surface disinfection practices on nosocomial pathogen exposures and infection risk can inform cleaning practices. The purpose of this study was to predict the effect of surface disinfection on viral infection risks and to determine needed viral reductions to achieve risk targets. Rotavirus, rhinovirus, and influenza A virus infection risks for two cases were modeled. Case 1 utilized a single fomite contact approach, while case 2 assumed 6 h of contact activities. A 94.1% viral reduction on surfaces and hands was measured following a single cleaning round using an Environmental Protection Agency (EPA)-registered disinfectant in an urgent care facility. This value was used to model the effect of a surface disinfection intervention on infection risk. Risk reductions for other surface-cleaning efficacies were also simulated. Surface reductions required to achieve risk probability targets were estimated. Under case 1 conditions, a 94.1% reduction in virus surface concentration reduced infection risks by 94.1%. Under case 2 conditions, a 94.1% reduction on surfaces resulted in median viral infection risks being reduced by 92.96 to 94.1% and an influenza A virus infection risk below one in a million. Surface concentration in the equations was highly correlated with dose and infection risk outputs. For rotavirus and rhinovirus, a >99.99% viral surface reduction would be needed to achieve a one-in-a-million risk target. This study quantifies reductions of infection risk relative to surface disinfectant use and demonstrates that risk targets for low-infectious-dose organisms may be more challenging to achieve. It is known that the use of EPA-registered surface disinfectant sprays can reduce infection risk if used according to the manufacturer's instructions. However, there are currently no standards for health care environments related to contamination levels on surfaces. The significance of this research is in quantifying needed reductions to meet various risk targets using realistic viral concentrations on surfaces for health care environments. This research informs the design of cleaning protocols by demonstrating that multiple applications may be needed to reduce risk and by highlighting a need for more models exploring the relationship among microbial contamination of surfaces, patient and health care worker behaviors, and infection risks.
Topics: Cross Infection; Disinfectants; Disinfection; Fomites; Humans; Influenza A virus; Influenza, Human; Models, Theoretical; Picornaviridae Infections; Rhinovirus; Risk Reduction Behavior; Rotavirus; Rotavirus Infections
PubMed: 29980557
DOI: 10.1128/AEM.00709-18 -
Viruses Mar 2023Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and...
Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air-liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55-75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50-80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (); acyl-CoA-binding, domain-containing (); and low-density lipoprotein receptor () genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment.
Topics: Humans; Pulmonary Surfactants; Rhinovirus; Epithelial Cells; Epithelium; Antiviral Agents; Enterovirus Infections; Lung; Lipids; Picornaviridae Infections
PubMed: 36992456
DOI: 10.3390/v15030747 -
PloS One 2013Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses...
Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses are genetically highly variable, and recombination between serotypes is known to be a major contribution to their diversity. Recently it was reported that recombination events in HRVs cause the diversity of HRV-C. This study analyzed parts of the viral genes spanning the 5' non- coding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. When analyzing parts of the 5'NCR and VP4/VP2 encoding sequences, we found intra- and interspecies recombinants in field strains of HRV-A and -C. Nineteen cases of recombination events (18.1%) were found among 105 field strains. For HRV-A, there were five cases (4.8%) of intraspecies recombination events and three cases (2.8%) of interspecies recombination events. For HRV-C, there were four cases (3.8%) of intraspecies recombination events and seven cases (6.7%) of interspecies recombination events. Recombination events were significantly more frequently observed in the ARINET samples (18 cases) than in the SLRI samples (1 case; P< 0.0001). The recombination breakpoints were located in nucleotides (nt) 472-554, which comprise stem-loop 5 in the internal ribosomal entry site (IRES), based on the HRV-B 35 sequence (accession no. FJ445187). Our findings regarding genomic recombination in circulating HRV-A and -C strains suggest that recombination might play a role in HRV fitness and could be a possible determinant of disease severity caused by various HRV infections in patients with ARI.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Humans; Infant; Middle Aged; Phylogeny; Picornaviridae Infections; Recombination, Genetic; Respiratory Tract Infections; Rhinovirus; Viral Proteins; Young Adult
PubMed: 23826363
DOI: 10.1371/journal.pone.0068081 -
Cureus Sep 2022Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with...
Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with the severity of acute illness. This study aimed to determine whether purUUpurU content correlates with virulence in other single-strand RNA (ssRNA) viruses that vary in clinical severity. Methodology We determined the copy number of purUUpurU in the genomes of two subtypes of human respiratory syncytial virus (RSV), respiratory syncytial virus A (RSV-A), and respiratory syncytial virus B (RSV-B), which vary in clinical severity. In addition, we determined the purUUpurU content of the four ebolaviruses that cause human disease, dengue virus, rabies virus, human rhinovirus-A, poliovirus type 1, astrovirus, rubella, yellow fever virus, and measles virus. Viral nucleotide sequence files were downloaded from the National Center for Biotechnology Information (NCBI)/National Institutes of Health website. In addition, we determined the cumulative case fatality rate of 20 epidemics of the Ebola virus and compared it with that of the other human ebolaviruses. Results The genomic purUUpurU content correlated with the severity of acute illness caused by both subtypes of RSV and human ebolaviruses. The lowest purUUpurU content was in the genome of the rubella virus, which causes mild disease. Conclusions The quantity of genomic purUUpurU is a virulence factor in ssRNA viruses. Blood hyperviscosity is one mechanism by which purUUpurU causes pathology. Comparative quantitative genomic analysis for purUUpurU will be helpful in estimating the risk posed by emergent ssRNA viruses.
PubMed: 36284814
DOI: 10.7759/cureus.29340 -
Frontiers in Immunology 2023Bacteria are well known to provide heterologous immunity against viral infections through various mechanisms including the induction of innate trained immunity and...
Bacteria are well known to provide heterologous immunity against viral infections through various mechanisms including the induction of innate trained immunity and adaptive cross-reactive immunity. Cross-reactive immunity from bacteria to viruses is responsible for long-term protection and yet its role has been downplayed due the difficulty of determining antigen-specific responses. Here, we carried out a systematic evaluation of the potential cross-reactive immunity from selected bacteria known to induce heterologous immunity against various viruses causing recurrent respiratory infections. The bacteria selected in this work were Bacillus Calmette Guerin and those included in the poly-bacterial preparation MV130: , , , , and . The virus included influenza A and B viruses, human rhinovirus A, B and C, respiratory syncytial virus A and B and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through BLAST searches, we first identified the shared peptidome space (identity ≥ 80%, in at least 8 residues) between bacteria and viruses, and subsequently predicted T and B cell epitopes within shared peptides. Interestingly, the potential epitope spaces shared between bacteria in MV130 and viruses are non-overlapping. Hence, combining diverse bacteria can enhance cross-reactive immunity. We next analyzed in detail the cross-reactive T and B cell epitopes between MV130 and influenza A virus. We found that MV130 contains numerous cross-reactive T cell epitopes with high population protection coverage and potentially neutralizing B cell epitopes recognizing hemagglutinin and matrix protein 2. These results contribute to explain the immune enhancing properties of MV130 observed in the clinic against respiratory viral infections.
Topics: Humans; Antiviral Agents; Influenza A virus; Epitopes, B-Lymphocyte; COVID-19; SARS-CoV-2; Bacteria; Vaccines
PubMed: 37675108
DOI: 10.3389/fimmu.2023.1235053 -
The Science of the Total Environment Oct 2023The effective detection of viruses in aircraft wastewater is crucial to establish surveillance programs for monitoring virus spread via aircraft passengers. This study...
The effective detection of viruses in aircraft wastewater is crucial to establish surveillance programs for monitoring virus spread via aircraft passengers. This study aimed to compare the performance of two virus concentration workflows, adsorption-extraction (AE) and Nanotrap® Microbiome A Particles (NMAP), in detecting the prevalence and concentrations of 15 endogenous viruses including ssDNA, dsDNA, ssRNA in 24 aircraft lavatory wastewater samples. The viruses tested included two indicator viruses, four enteric viruses, and nine respiratory viruses. The results showed that cross-assembly phage (crAssphage), human polyomavirus (HPyV), rhinovirus A (RhV A), and rhinovirus B (RhV B) were detected in all wastewater samples using both workflows. However, enterovirus (EV), human norovirus GII (HNoV GII), human adenovirus (HAdV), bocavirus (BoV), parechovirus (PeV), epstein-barr virus (EBV). Influenza A virus (IAV), and respiratory syncytial virus B (RsV B) were infrequently detected by both workflows, and hepatitis A virus (HAV), influenza B virus (IBV), and respiratory syncytial virus B (RsV A) were not detected in any samples. The NMAP workflow had greater detection rates of RNA viruses (EV, PeV, and RsV B) than the AE workflow, while the AE workflow had greater detection rates of DNA viruses (HAdV, BoV, and EBV) than the NMAP workflow. The concentration of each virus was also analyzed, and the results showed that crAssphage had the highest mean concentration (6.76 log GC/12.5 mL) followed by HPyV (5.46 log GC/12.5 mL using the AE workflow, while the mean concentrations of enteric and respiratory viruses ranged from 2.48 to 3.63 log GC/12.5 mL. Using the NMAP workflow, the mean concentration of crAssphage was 5.18 log GC/12.5 mL and the mean concentration of HPyV was 4.20 log GC/12.5 mL, while mean concentrations of enteric and respiratory viruses ranged from 2.55 to 3.74 log GC/12.5 mL. Significantly higher (p < 0.05) mean concentrations of crAssphage and HPyV were observed when employing the AE workflow in comparison to the NMAP workflow. Conversely, the NMAP workflow yielded significantly greater (p < 0.05) concentrations of RhV A, and RhV B compared to the AE workflow. The findings of this study can aid in the selection of an appropriate concentration workflow for virus surveillance studies and contribute to the development of efficient virus detection methods.
Topics: Humans; Wastewater; Workflow; Adsorption; Epstein-Barr Virus Infections; Toilet Facilities; Herpesvirus 4, Human; Microbiota; Bacteriophages; Polyomavirus; Adenoviruses, Human
PubMed: 37348715
DOI: 10.1016/j.scitotenv.2023.165007 -
The Science of the Total Environment Mar 2023The early warning and tracking of COVID-19 prevalence in the community provided by wastewater surveillance has highlighted its potential for much broader viral disease...
The early warning and tracking of COVID-19 prevalence in the community provided by wastewater surveillance has highlighted its potential for much broader viral disease surveillance. In this proof-of-concept study, 46 wastewater samples from four wastewater treatment plants (WWTPs) in Queensland, Australia, were analyzed for the presence and abundance of 13 respiratory viruses, and the results were compared with reported clinical cases. The viruses were concentrated using the adsorption-extraction (AE) method, and extracted nucleic acids were analyzed using qPCR and RT-qPCR. Among the viruses tested, bocavirus (BoV), parechovirus (PeV), rhinovirus A (RhV A) and rhinovirus B (RhV B) were detected in all wastewater samples. All the tested viruses except influenza B virus (IBV) were detected in wastewater sample from at least one WWTP. BoV was detected with the greatest concentration (4.96-7.22 log GC/L), followed by Epstein-Barr virus (EBV) (4.08-6.46 log GC/L), RhV A (3.95-5.63 log GC/L), RhV B (3.74-5.61 log GC/L), and PeV (3.17-5.32 log GC/L). Influenza viruses and respiratory syncytial virus (RSV) are notifiable conditions in Queensland, allowing the gene copy (GC) concentrations to be compared with reported clinical cases. Significant correlations (ρ = 0.60, p < 0.01 for IAV and ρ = 0.53, p < 0.01 for RSV) were observed when pooled wastewater influenza A virus (IAV) and RSV log GC/L concentrations were compared to log clinical cases among the four WWTP catchments. The positive predictive value for the presence of IAV and RSV in wastewater was 97 % for both IAV and RSV clinical cases within the four WWTP catchments. The overall accuracy of wastewater analysis for predicting clinical cases of IAV and RSV was 97 and 90 %, respectively. This paper lends credibility to the application of wastewater surveillance to monitor respiratory viruses of various genomic characteristics, with potential uses for increased surveillance capabilities and as a tool in understanding the dynamics of disease circulation in the communities.
Topics: Humans; Wastewater; Queensland; Epstein-Barr Virus Infections; Herpesvirus 4, Human; COVID-19; Wastewater-Based Epidemiological Monitoring; Respiratory Syncytial Viruses; Influenza B virus; Australia; Influenza, Human
PubMed: 36539100
DOI: 10.1016/j.scitotenv.2022.161023 -
Viruses Nov 2022Viral respiratory infections contribute to significant morbidity and mortality in children. Currently, there are limited reports on the composition and abundance of the...
Metagenomic Analysis of Respiratory RNA Virome of Children with and without Severe Acute Respiratory Infection from the Free State, South Africa during COVID-19 Pandemic Reveals Higher Diversity and Abundance in Summer Compared with Winter Period.
Viral respiratory infections contribute to significant morbidity and mortality in children. Currently, there are limited reports on the composition and abundance of the normal commensal respiratory virome in comparison to those in severe acute respiratory infections (SARIs) state. This study characterised the respiratory RNA virome in children ≤ 5 years with (n = 149) and without (n = 139) SARI during the summer and winter of 2020/2021 seasons in South Africa. Nasopharyngeal swabs were, collected, pooled, enriched for viral RNA detection, sequenced using Illumina MiSeq, and analysed using the Genome Detective bioinformatic tool. Overall, , , , , , and families were the most abundant viral population in both groups across both seasons. Human rhinovirus and endogenous retrovirus K113 were detected in most pools, with exclusive detection of in SARI pools. Generally, higher viral diversity/abundance was seen in children with SARI and in the summer pools. Several plant/animal viruses, eukaryotic viruses with unclear pathogenicity including a distinct rhinovirus A type, were detected. This study provides remarkable data on the respiratory RNA virome in children with and without SARI with a degree of heterogeneity of known viruses colonizing their respiratory tract. The implication of the detected viruses in the dynamics/progression of SARI requires further investigations.
Topics: Child; Animals; Humans; Virome; South Africa; COVID-19; Seasons; RNA; Pandemics; Respiratory Tract Infections; Pneumonia; Viruses; Respiratory System
PubMed: 36423125
DOI: 10.3390/v14112516 -
American Journal of Respiratory and... Oct 2017Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.
RATIONALE
Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.
OBJECTIVES
To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.
METHODS
In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.
MEASUREMENTS AND MAIN RESULTS
RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).
CONCLUSIONS
In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).
Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Child; Female; Humans; Male; Omalizumab; Rhinovirus; United States; Virus Diseases
PubMed: 28608756
DOI: 10.1164/rccm.201701-0120OC -
Viruses Aug 2022Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite...
Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite important evidence on the role of RV reported by clinicians and life scientists, there are still unanswered questions regarding their influence on asthma exacerbation in young patients. Thus, we measured the RVspecies-specific IgG titers in our German pediatric exacerbation cohort using a microarray-based technology. For this approach, human sera of patients with exacerbated asthma and wheeze, as well as healthy control subjects ( = 136) were included, and correlation analyses were performed. Concordantly with previously published results, we observed significantly higher cumulative levels of RV species A-specific IgG ( = 0.011) and RV-C-specific IgG ( = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A ( = 0.0011) and species C ( = 0.0009) compared to non-atopic wheezers. Hypothesizing that bacterial infection positively correlates with immune memory against RV, we included nasopharyngeal swab results in our analyses and detected limited correlations. Interestingly, the eosinophil blood titer positively correlated with RV-specific IgG levels. With these observations, we add important observations to the existing data regarding exacerbation in pediatric and adolescent medicine. We propose that scientists and clinicians should pay more attention to the relevance of RV species in susceptible pediatric patients.
Topics: Adolescent; Antibody Formation; Asthma; Child; Enterovirus Infections; Humans; Immunoglobulin G; Picornaviridae Infections; Rhinovirus
PubMed: 36146664
DOI: 10.3390/v14091857