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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 -
The Journal of Infectious Diseases Aug 2018Despite the frequency of human rhinovirus (HRV), data describing the molecular epidemiology of HRV in the community are limited. Childcare centers are optimal settings...
BACKGROUND
Despite the frequency of human rhinovirus (HRV), data describing the molecular epidemiology of HRV in the community are limited. Childcare centers are optimal settings to characterize heterotypic HRV cocirculation.
METHODS
HRV specimens were prospectively obtained from a cohort of childcare attendees at enrollment and weekly during respiratory illness. The 5' noncoding region sequences were used to determine HRV species (A, B, C) and genotypes.
RESULTS
Among 225 children followed, sequence data were available for 92 HRV infections: HRV-A (n = 80; 59%) was most common, followed by HRV-C (n = 52, 39%), and HRV-B (n = 3, 2%). Forty-one genotypes were identified and cocirculation was common. Frequent spread between classrooms occurred with 2 HRV-A genotypes. Repeated detections within single illnesses were a combination of persistent (n = 7) and distinct (n = 7) genotypes. Prevalence of HRV among asymptomatic children was 41%. HRV-C was clinically similar to HRV-A and HRV-B.
CONCLUSIONS
HRV epidemiology in childcare consists of heterotypic cocirculation of genotypes with periodic spread within and among classrooms. Based on our finding of multiple genotypes evident during the course of single illnesses, the use of sequence-based HRV type determination is critical in longitudinal studies of HRV epidemiology and transmission.
Topics: Child Day Care Centers; Child, Preschool; Cross-Sectional Studies; Enterovirus; Female; Genotype; Genotyping Techniques; Humans; Infant; Male; Phylogeny; Picornaviridae Infections; Prevalence; RNA, Viral; Respiratory Tract Infections; Rhinovirus; Sequence Analysis, RNA
PubMed: 29684211
DOI: 10.1093/infdis/jiy232 -
The Journal of Infectious Diseases Aug 2018
Topics: Enterovirus; Enterovirus Infections; Humans; Respiratory Tract Infections; Rhinovirus
PubMed: 29684193
DOI: 10.1093/infdis/jiy233 -
Scientific Reports Apr 2018The overall non-neutralizing antibody responses against EV infections among infants and children remain unknown. The non-neutralizing antibody responses against VP1 of...
The overall non-neutralizing antibody responses against EV infections among infants and children remain unknown. The non-neutralizing antibody responses against VP1 of EV-A species (Enterovirus 71 (EV71), Coxsackievirus A16 (CA16)), EV-B species (Coxsackievirus B3 (CB3)), EV-C species (Poliovirus 1 (PV1)) and RV-A species (Rhinovirus A N13 (RV13)) were detected and analyzed using a novel evolved immunoglobulin-binding molecule (NEIBM)-based ELISA among infants and children aged 1 day to 6 years in Shanghai. The anti-VP1 reactivity against these EVs changed similarly in an age-related dynamic: being high level in the 1-28-day age group, declining to the lowest level in the 1-12-month age group, gradually increasing to the peak level in the 13-60-month age group, and remarkably declining in the 61-72-month age group, which reflects the conversion from maternally-derived to primary antibody responses. The anti-RV13 VP1 antibodies were demonstrated at the highest level, with anti-CB3 and PV1 VP1 antibodies at the second highest level and anti-CA16 and EV71 VP1 antibodies at the lowest level. These findings are the first to describe the overall non-neutralizing antibody responses against VP1 of the EV-A, B, C and RV-A viruses among the infants and children and could be helpful for further understanding the ubiquitous EV infections among children.
Topics: Antibodies, Viral; Capsid Proteins; Child; Child, Preschool; China; Enterovirus; Female; Humans; Infant; Infant, Newborn; Male; Recombinant Proteins
PubMed: 29615683
DOI: 10.1038/s41598-018-23683-x -
Planta Medica Jul 2018In this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented....
In this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation of predictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an IC threshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.
Topics: Acute Disease; Agaricales; Animals; Antiviral Agents; Biological Products; Dogs; Drug Discovery; Enterovirus; Enterovirus B, Human; Ethnopharmacology; Female; HeLa Cells; Humans; Influenza A Virus, H3N2 Subtype; Inhibitory Concentration 50; Madin Darby Canine Kidney Cells; Phenotype; Plants; Respiratory Tract Infections
PubMed: 29554706
DOI: 10.1055/a-0590-5153 -
The Journal of Infectious Diseases Jan 2018Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked circulating CD4+ T cells with identical epitope specificities that responded to intranasal challenge with rhinovirus (RV)-A39, and we assessed T-cell signatures in the nose.
METHODS
Cells were monitored using a mixture of 2 capsid-specific major histocompatibility complex II tetramers over a 7-week period, before and after RV-A39 challenge, in 16 human leukocyte antigen-DR4+ subjects who participated in a trial of Bifidobacterium lactis (Bl-04) supplementation.
RESULTS
Pre-existing tetramer+ T cells were linked to delayed viral shedding, enriched for activated CCR5+ Th1 effectors, and included a minor interleukin-21+ T follicular helper cell subset. After RV challenge, expansion and activation of virus-specific CCR5+ Th1 effectors was restricted to subjects who had a rise in neutralizing antibodies, and tetramer-negative CCR5+ effector memory types were comodulated. In the nose, CXCR3-CCR5+ T cells present during acute infection were activated effector memory type, whereas CXCR3+ cells were central memory type, and cognate chemokine ligands were elevated over baseline. Probiotic had no T-cell effects.
CONCLUSIONS
We conclude that virus-specific CCR5+ effector memory CD4+ T cells primed by previous exposure to related viruses contribute to the control of rhinovirus.
Topics: Adolescent; Adult; Blood; Cell Tracking; Enterovirus; Enterovirus Infections; Female; Humans; Immunologic Memory; Male; Middle Aged; Nasal Mucosa; Receptors, CCR5; Th1 Cells; Young Adult
PubMed: 29309618
DOI: 10.1093/infdis/jix514 -
BMC Infectious Diseases Dec 2017Unlike influenza viruses, little is known about the prevalence and seasonality of other respiratory viruses because laboratory surveillance for non-influenza respiratory...
BACKGROUND
Unlike influenza viruses, little is known about the prevalence and seasonality of other respiratory viruses because laboratory surveillance for non-influenza respiratory viruses is not well developed or supported in China and other resource-limited countries. We studied the interference between seasonal epidemics of influenza viruses and five other common viruses that cause respiratory illnesses in Hong Kong from 2014 to 2017.
METHODS
The weekly laboratory-confirmed positive rates of each virus were analyzed from 2014 to 2017 in Hong Kong to describe the epidemiological trends and interference between influenza viruses, respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus, enterovirus and rhinovirus. A sinusoidal model was established to estimate the peak timing of each virus by phase angle parameters.
RESULTS
Seasonal features of the influenza viruses, PIV, enterovirus and adenovirus were obvious, whereas annual peaks of RSV and rhinovirus were not observed. The incidence of the influenza viruses usually peaked in February and July, and the summer peaks in July were generally caused by the H3 subtype of influenza A alone. When influenza viruses were active, other viruses tended to have a low level of activity. The peaks of the influenza viruses were not synchronized. An epidemic of rhinovirus tended to shift the subsequent epidemics of the other viruses.
CONCLUSION
The evidence from recent surveillance data in Hong Kong suggests that viral interference during the epidemics of influenza viruses and other common respiratory viruses might affect the timing and duration of subsequent epidemics of a certain or several viruses.
Topics: Adenoviridae; Child, Preschool; Enterovirus; Epidemics; Hong Kong; Humans; Incidence; Influenza, Human; Nasopharynx; Orthomyxoviridae; Pharynx; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Rhinovirus; Rubulavirus; Seasons
PubMed: 29246199
DOI: 10.1186/s12879-017-2888-5 -
Immunity, Inflammation and Disease Mar 2018Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic... (Clinical Trial)
Clinical Trial
BACKGROUND
Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined.
OBJECTIVE
The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls.
METHODS
A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C.
RESULTS
Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C.
CONCLUSIONS AND CLINICAL RELEVANCE
The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections.
Topics: Adolescent; Asthma; Child; Child, Preschool; Coxsackievirus Infections; Enterovirus; Female; Humans; Immunologic Memory; Infant; Male; T-Lymphocytes, Regulatory
PubMed: 29124902
DOI: 10.1002/iid3.206 -
Journal of Investigative Medicine High... 2017A 22-year-old Asian woman presented with respiratory distress, cough, and wheezing for 1 week. Prior history included asthma and Turner syndrome. On presentation to the...
A 22-year-old Asian woman presented with respiratory distress, cough, and wheezing for 1 week. Prior history included asthma and Turner syndrome. On presentation to the emergency department, the patient was hypotensive, tachycardic, tachypneic, with an oxyhemoglobin saturation in the mid 80% range while breathing ambient air. Chest radiograph revealed pulmonary vascular congestion and a left lower lobe infiltrate. Endotracheal intubation, mechanical ventilation, and vasopressors were initiated. Empiric therapy for community-acquired pneumonia was administered utilizing broad-spectrum intravenous antibiotics. Routine sputum culture was negative for pathogens. Nasopharyngeal swab submitted for multiplex amplified nucleic acid testing yielded enterovirus-human rhinovirus (EV-HRV). Thus, the diagnosis of EV-HRV pneumonia complicated by acute respiratory distress syndrome (ARDS) was established. Multiple attempts to wean from the ventilator were unsuccessful, and a tracheostomy was performed. This report highlights EV-HRV as a cause of severe ARDS and prolonged respiratory failure in adults.
PubMed: 28904980
DOI: 10.1177/2324709617728526 -
PloS One 2017Non-bacterial acute gastroenteritis (AGE) associated with virus infection affects individuals living in developing countries, especially children. To investigate whether...
Non-bacterial acute gastroenteritis (AGE) associated with virus infection affects individuals living in developing countries, especially children. To investigate whether shedding of certain human enterovirus (EV) is more frequently detected in the stool of individuals with AGE of unknown etiology than individuals without AGE symptoms, we tested fecal samples collected from 2,692 individuals with diarrhea between January 2010 and December 2016. Samples were tested for rotavirus, norovirus, and EV by reverse-transcription polymerase chain reaction (RT-PCR) and adenovirus by PCR. EV-positive samples were subjected to sequencing and phylogenetic analysis to identify EV species and types. Findings were compared to EV found in 1,310 fecal samples from individuals without AGE who were diagnosed with hand, foot, and mouth disease (HFMD). While the majority of viruses identified in AGE consisted of human rotavirus (22.7%), norovirus (11.4%) and adenovirus (9.3%), we identified EV (6.2%) belonging mainly to species B, C, and rhinovirus. In contrast, >92% of EV found without AGE symptoms belonged to species A. Although AGE symptoms are not often attributed to EV infection, EV was associated with diarrhea of unknown etiology at least in 3.4% of AGE cases. While CV-A6 was most likely to be found in stools of HFMD patients, rhinovirus A and C were the two most common EV species associated with AGE. Elucidating group-specific EV infection in diseases with and without AGE will be useful in assisting identification, clinical management, and the surveillance of EV infection in the community.
Topics: Acute Disease; Adolescent; Base Sequence; Child; Child, Preschool; Cohort Studies; Diarrhea; Enterovirus; Enterovirus Infections; Female; Gastroenteritis; Genotype; Hand, Foot and Mouth Disease; Humans; Male; Phylogeny; Thailand
PubMed: 28750058
DOI: 10.1371/journal.pone.0182078