Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection.

PubMed

Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E

2017-07-01

We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection

PubMed Central

Jung, Hwa Sik; Kang, Byung Ju; Ra, Seung Won; Seo, Kwang Won; Jegal, Yangjin; Jun, Jae-Bum; Jung, Jiwon; Jeong, Joseph; Jeon, Hee-Jeong; Ahn, Jae-Sung

2017-01-01

Background Bacterial pneumonia occurring after respiratory viral infection is common. However, the predominant bacterial species causing pneumonia secondary to respiratory viral infections other than influenza remain unknown. The purpose of this study was to know whether the pathogens causing post-viral bacterial pneumonia vary according to the type of respiratory virus. Methods Study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital between April 2013 and March 2016. The patients' medical records were retrospectively reviewed. Results A total of 251 clinically significant bacteria were identified in 233 patients with post-viral bacterial pneumonia. Mycoplasma pneumoniae was the most frequent bacterium in patients aged <16 years, regardless of the preceding virus type (p=0.630). In patients aged ≥16 years, the isolated bacteria varied according to the preceding virus type. The major results were as follows (p<0.001): pneumonia in patients with influenza virus (type A/B), rhinovirus, and human metapneumovirus infections was caused by similar bacteria, and the findings indicated that Staphylococcus aureus pneumonia was very common in these patients. In contrast, coronavirus, parainfluenza virus, and respiratory syncytial virus infections were associated with pneumonia caused by gram-negative bacteria. Conclusion The pathogens causing post-viral bacterial pneumonia vary according to the type of preceding respiratory virus. This information could help in selecting empirical antibiotics in patients with post-viral pneumonia. PMID:28905531

Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

PubMed

Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

2018-01-01

Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Metagenomic analysis of viral diversity in respiratory samples from patients with respiratory tract infections in Kuwait.

PubMed

Madi, Nada; Al-Nakib, Widad; Mustafa, Abu Salim; Habibi, Nazima

2018-03-01

A metagenomic approach based on target independent next-generation sequencing has become a known method for the detection of both known and novel viruses in clinical samples. This study aimed to use the metagenomic sequencing approach to characterize the viral diversity in respiratory samples from patients with respiratory tract infections. We have investigated 86 respiratory samples received from various hospitals in Kuwait between 2015 and 2016 for the diagnosis of respiratory tract infections. A metagenomic approach using the next-generation sequencer to characterize viruses was used. According to the metagenomic analysis, an average of 145, 019 reads were identified, and 2% of these reads were of viral origin. Also, metagenomic analysis of the viral sequences revealed many known respiratory viruses, which were detected in 30.2% of the clinical samples. Also, sequences of non-respiratory viruses were detected in 14% of the clinical samples, while sequences of non-human viruses were detected in 55.8% of the clinical samples. The average genome coverage of the viruses was 12% with the highest genome coverage of 99.2% for respiratory syncytial virus, and the lowest was 1% for torque teno midi virus 2. Our results showed 47.7% agreement between multiplex Real-Time PCR and metagenomics sequencing in the detection of respiratory viruses in the clinical samples. Though there are some difficulties in using this method to clinical samples such as specimen quality, these observations are indicative of the promising utility of the metagenomic sequencing approach for the identification of respiratory viruses in patients with respiratory tract infections. © 2017 Wiley Periodicals, Inc.

Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infection in Humans

PubMed Central

Zaas, Aimee K.; Chen, Minhua; Varkey, Jay; Veldman, Timothy; Hero, Alfred O.; Lucas, Joseph; Huang, Yongsheng; Turner, Ronald; Gilbert, Anthony; Lambkin-Williams, Robert; Øien, N. Christine; Nicholson, Bradly; Kingsmore, Stephen; Carin, Lawrence; Woods, Christopher W.; Ginsburg, Geoffrey S.

2010-01-01

Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals. PMID:19664979

Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

PubMed Central

McCarthy, Mary K.; Weinberg, Jason B.

2012-01-01

Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection. PMID:22665949

Promising approaches for the treatment and prevention of viral respiratory illnesses.

PubMed

Papadopoulos, Nikolaos G; Megremis, Spyridon; Kitsioulis, Nikolaos A; Vangelatou, Olympia; West, Peter; Xepapadaki, Paraskevi

2017-10-01

Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Respiratory viral infections in infants with clinically suspected pertussis.

PubMed

Ferronato, Angela E; Gilio, Alfredo E; Vieira, Sandra E

2013-01-01

to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Genetic associations with viral respiratory illnesses and asthma control in children

PubMed Central

Loisel, Dagan A; Du, Gaixin; Ahluwalia, Tarunveer Singh; Tisler, Christopher J.; Evans, Michael D.; Myers, Rachel A.; Gangnon, Ronald E.; Kreiner-Møller, Eskil; Bønnelykke, Klaus; Bisgaard, Hans; Jackson, Daniel J.; Lemanske, Robert F.; Nicolae, Dan L.; Gern, James E.; Ober, Carole

2015-01-01

Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma. PMID:26399222

Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT.

PubMed

Haak, Bastiaan W; Littmann, Eric R; Chaubard, Jean-Luc; Pickard, Amanda J; Fontana, Emily; Adhi, Fatima; Gyaltshen, Yangtsho; Ling, Lilan; Morjaria, Sejal M; Peled, Jonathan U; van den Brink, Marcel R; Geyer, Alexander I; Cross, Justin R; Pamer, Eric G; Taur, Ying

2018-04-19

Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HSCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S rRNA sequencing to determine microbiota composition and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate producing bacteria were a five-fold less likely to develop viral LRTI, independent of other factors (adjusted HR=0.22, 95% CI 0.04 - 0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients. Copyright © 2018 American Society of Hematology.

The presence of fever in adults with influenza and other viral respiratory infections.

PubMed

Chughtai, A A; Wang, Q; Dung, T C; Macintyre, C R

2017-01-01

We compared the rates of fever in adult subjects with laboratory-confirmed influenza and other respiratory viruses and examined the factors that predict fever in adults. Symptom data on 158 healthcare workers (HCWs) with a laboratory-confirmed respiratory virus infection were collected using standardized data collection forms from three separate studies. Overall, the rate of fever in confirmed viral respiratory infections in adult HCWs was 23·4% (37/158). Rates varied by virus: human rhinovirus (25·3%, 19/75), influenza A virus (30%, 3/10), coronavirus (28·6%, 2/7), human metapneumovirus (28·6%, 2/7), respiratory syncytial virus (14·3%, 4/28) and parainfluenza virus (8·3%, 1/12). Smoking [relative risk (RR) 4·65, 95% confidence interval (CI) 1·33-16·25] and co-infection with two or more viruses (RR 4·19, 95% CI 1·21-14·52) were significant predictors of fever. Fever is less common in adults with confirmed viral respiratory infections, including influenza, than described in children. More than 75% of adults with a viral respiratory infection do not have fever, which is an important finding for clinical triage of adult patients with respiratory infections. The accepted definition of 'influenza-like illness' includes fever and may be insensitive for surveillance when high case-finding is required. A more sensitive case definition could be used to identify adult cases, particularly in event of an emerging viral infection.

Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

PubMed Central

Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

2015-01-01

Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

PubMed

Kim, Young-In; Murphy, Ryan; Majumdar, Sirshendu; Harrison, Lisa G; Aitken, Jody; DeVincenzo, John P

2015-10-01

Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

Viral coinfection in childhood respiratory tract infections.

PubMed

Martínez-Roig, A; Salvadó, M; Caballero-Rabasco, M A; Sánchez-Buenavida, A; López-Segura, N; Bonet-Alcaina, M

2015-01-01

The introduction of molecular techniques has enabled better understanding of the etiology of respiratory tract infections in children. The objective of the study was to analyze viral coinfection and its relationship to clinical severity. Hospitalized pediatric patients with a clinical diagnosis of respiratory infection were studied during the period between 2009-2010. Clinical and epidemiological data, duration of hospitalization, need for oxygen therapy, bacterial coinfection and need for mechanical ventilation were collected. Etiology was studied by multiplex PCR and low-density microarrays for 19 viruses. A total of 385 patients were positive, 44.94% under 12 months. The most frequently detected viruses were RSV-B: 139, rhinovirus: 114, RSV-A: 111, influenza A H1N1-2009: 93 and bocavirus: 77. Coinfection was detected in 61.81%, 36.36% with 2 viruses, 16.10% and 9.35% with 3 to 4 or more. Coinfection was higher in 2009 with 69.79 vs. 53.88% in 2010. Rhinovirus/RSV-B on 10 times and RSV-A/RSV-B on 5 times were the most detected coinfections. Hospitalization decreased with greater number of viruses (P<0,001). Oxygen therapy was required by 26.75% (one virus was detected in 55.34% of cases). A larger number of viruses resulted in less need for oxygen (P<0,001). Ten cases required mechanical ventilation, 4 patients with bacterial coinfection and 5 with viral coinfection (P=0,69). An inverse relationship was found between the number of viruses detected in nasopharyngeal aspirate, the need for oxygen therapy and hospitalization days. More epidemiological studies and improved quantitative detection techniques are needed to define the role of viral coinfections in respiratory disease and its correlation with the clinical severity. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

[Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

PubMed

Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

2017-04-12

Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

PubMed

Kuo, Elbert; Bharat, Ankit; Goers, Trudie; Chapman, Will; Yan, Le; Street, Tyler; Lu, Wei; Walter, Michael; Patterson, Alexander; Mohanakumar, Thalachallour

2006-09-01

The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

PubMed

Galván, José María; Rajas, Olga; Aspa, Javier

2015-11-01

Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

The Tennessee Children's Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases.

PubMed

Hartert, Tina V; Carroll, Kecia; Gebretsadik, Tebeb; Woodward, Kimberly; Minton, Patricia

2010-05-01

The 'attack rate' of asthma following viral lower respiratory tract infections (LRTI) is about 3-4 fold higher than that of the general population; however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Children's Respiratory Initiative has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long-term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on early childhood outcomes. Over four respiratory viral seasons, 2004–2008, term, predominantly non-low weight previously healthy infants and their biological mothers were enrolled during an infant's acute viral respiratory illness.Longitudinal follow up to age 6 years is ongoing [corrected]. This report describes the study objectives, design and recruitment results of the over 650 families enrolled in this longitudinal investigation. The Tennessee Children's Respiratory Initiative is additionally unique because it is designed in parallel with a large retrospective birth cohort of over 95,000 mother-infant dyads with similar objectives to investigate the role of respiratory viral infection severity and aetiology in the development of asthma. Future reports from this cohort will help to clarify the complex relationship between infant respiratory viral infection severity, aetiology, atopic predisposition and the subsequent development of early childhood asthma and atopic diseases.

Respiratory viral coinfection and disease severity in children: A systematic review and meta-analysis.

PubMed

Scotta, Marcelo Comerlato; Chakr, Valentina Coutinho Baldoto Gava; de Moura, Angela; Becker, Rafaela Garces; de Souza, Ana Paula Duarte; Jones, Marcus Herbert; Pinto, Leonardo Araújo; Sarria, Edgar Enrique; Pitrez, Paulo Marcio; Stein, Renato Tetelbom; Mattiello, Rita

2016-07-01

With advent of molecular diagnostic technologies, studies have reported detection of two or more respiratory viruses in about 30% of children with respiratory infections. However, prognostic role of coinfection remains unclear. Evaluate relation between respiratory viral confection and illness severity in children. MEDLINE (through PUBMED), EMBASE, EBSCO, LILACS databases were searched up to March 2015 by two independent reviewers. Studies assessing severity of viral coinfection in patients aged less than 18 years were included. Standardized forms were used for data extraction of population, study design, clinical syndromes, virus combinations compared and severity outcomes. Risk of bias and quality of evidence were assessed through EPHPP and GRADE. Subgroup analysis was performed according to age and viral combinations. Of 5218 records screened, 43 were included in analysis. Viral coinfection did not influence risks of all outcomes assessed: length of stay (mean difference in days in coinfection, -0.10 [95% confidence interval: -0.51 to 0.31]), length of supplemental oxygen (-0.42 [-1.05 to 0.20]), need of hospitalization (odds ratio of coinfection, 0.96 [95% confidence interval: 0.61-1.51]), supplemental oxygen (0.94 [0.66 to 1.34]), need of intensive care (0.99 [0.64 to 1.54]), mechanical ventilation (0.81 [0.33 to 2.01]) and death (2.22 [0.83 to 5.95]). Sub-analyses according to age and viral combinations have not shown influence of these factors in outcomes. Respiratory viral coinfection did not increase severity in all outcomes assessed. Further studies are necessary to confirm this finding, especially regarding role of specific viral interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of the viral respiratory season on postoperative outcomes in children undergoing cardiac surgery.

PubMed

Spaeder, Michael C; Carson, Kathryn A; Vricella, Luca A; Alejo, Diane E; Holmes, Kathryn W

2011-08-01

To compare postoperative outcomes in children undergoing cardiac surgery during the viral respiratory season and nonviral season at our institution. This was a retrospective cohort study and secondary matched case-control analysis. The setting was an urban academic tertiary-care children's hospital. The study was comprised of all patients <18 years of age who underwent cardiac surgery at Johns Hopkins Hospital from October 2002 through September 2007. Patients were stratified by season of surgery, complexity of cardiac disease, and presence or absence of viral respiratory infection. Measurements included patient characteristics and postoperative outcomes. The primary outcome was postoperative length of stay (LOS). A total of 744 patients were included in the analysis. There was no difference in baseline characteristics or outcomes, specifically, no difference in postoperative LOS, intensive care unit (ICU) LOS, and mortality, among patients by seasons of surgery. Patients with viral respiratory illness were more likely to have longer postoperative LOS (p < 0.01) and ICU LOS (p < 0.01) compared with matched controls. We identified no difference in postoperative outcomes based on season in patients undergoing cardiac surgery. Children with viral respiratory infection have significantly worse outcomes than matched controls, strengthening the call for universal administration of influenza vaccination and palivizumab to appropriate groups. Preoperative testing for respiratory viruses should be considered during the winter months for children undergoing elective cardiac surgery.

Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection

PubMed Central

Giuffrida, María J; Valero, Nereida; Mosquera, Jesús; Alvarez de Mon, Melchor; Chacín, Betulio; Espina, Luz Marina; Gotera, Jennifer; Bermudez, John; Mavarez, Alibeth

2014-01-01

Background Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. Objectives The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. Patients/Methods Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. Results Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. Conclusions Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections. PMID:23962134

A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China.

PubMed

He, Ying; Lin, Guang-Yu; Wang, Qiong; Cai, Xiao-Ying; Zhang, Yin-Hui; Lin, Chuang-Xing; Lu, Chang-Dong; Lu, Xue-Dong

2014-07-01

The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small-medium cities and rural areas. To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. Of the 2025 children enrolled in the study, 971 (48.0%) were positive for at least one viral pathogen, in which 890 (91.7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35.8%), respiratory syncytial virus (RSV; 30.5%) and human rhinovirus (HRV; 21.5%). Co-infections were found in 302 cases (31.1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection

PubMed Central

Zaas, Aimee K.; Burke, Thomas; Chen, Minhua; McClain, Micah; Nicholson, Bradly; Veldman, Timothy; Tsalik, Ephraim L.; Fowler, Vance; Rivers, Emanuel P.; Otero, Ronny; Kingsmore, Stephen F.; Voora, Deepak; Lucas, Joseph; Hero, Alfred O.; Carin, Lawrence; Woods, Christopher W.; Ginsburg, Geoffrey S.

2014-01-01

Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR–based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting. PMID:24048524

Respiratory Viral Detections During Symptomatic and Asymptomatic Periods in Young Andean Children

PubMed Central

Howard, Leigh M.; Johnson, Monika; Williams, John V.; Zhu, Yuwei; Gil, Ana I.; Edwards, Kathryn M.; Griffin, Marie R.; Lanata, Claudio F.; Grijalva, Carlos G.

2015-01-01

Background Viruses are commonly detected in children with acute respiratory illnesses (ARI) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate interpretation of viral detections but are currently scant. Methods We used reverse transcription-polymerase chain reaction (RT-PCR) to analyze respiratory samples from young Andean children for viruses during asymptomatic periods within 8-120 days of index ARI (cough or fever). We compared viral detections over time within children and explored RT-PCR cycle thresholds (CT) as surrogates for viral loads. Results At least one respiratory virus was detected in 367 (43%) of 859 samples collected during asymptomatic periods, with more frequent detections in periods with rhinorrhea (49%) than those without (34%, p<0.001). Relative to index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory syncytial virus (RSV), and parainfluenza virus (PIV) detected, the same virus was also detected during 32%, 22%, 10%, and 3% of asymptomatic periods, respectively. RSV was only detected 8-30 days after index RSV ARI, whereas HRV and AdV were detected throughout asymptomatic periods. Human metapneumovirus (MPV) and influenza were rarely detected during asymptomatic periods (<3%). No significant differences were observed in the CT for HRV or AdV during asymptomatic periods relative to ARI. For RSV, CT were significantly lower during ARI relative to the asymptomatic period (p=0.03). Conclusions These findings indicate that influenza, MPV, PIV, and RSV detections in children with ARI usually indicate a causal relationship. When HRV or AdV is detected during ARI, the causal relationship is less certain. PMID:26121205

Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

PubMed Central

Schlapbach, Luregn J.; Anchisi, Stéphanie; Hammer, Christian; Bartha, Istvan; Junier, Thomas; Mottet-Osman, Geneviève; Posfay-Barbe, Klara M.; Longchamp, David; Stocker, Martin; Cordey, Samuel; Kaiser, Laurent; Riedel, Thomas; Kenna, Tony; Long, Deborah; Schibler, Andreas; Tapparel, Caroline; Garcin, Dominique

2017-01-01

Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses. PMID:28716935

Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

PubMed

Shapiro, David; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Hsiang, Jeremy; Nicholson, Bradley; De Silva, Aruna Dharshan; Østbye, Truls; Reller, Megan E; Woods, Christopher W; Tillekeratne, L Gayani

2017-07-01

In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% ( N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children

PubMed Central

Mazur, Natalie I.; Bont, Louis; Cohen, Adam L.; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J.; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K.; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A.

2017-01-01

Background Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Methods Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009–December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Results Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)–associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39–1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6–7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0–4.5; P = .05) compared with RSV monoinfection. Conclusions RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. PMID:27927871

Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines.

PubMed

Kadji, Francois Marie Ngako; Okamoto, Michiko; Furuse, Yuki; Tamaki, Raita; Suzuki, Akira; Lirio, Irene; Dapat, Clyde; Malasao, Rungnapa; Saito, Mariko; Pedrera-Rico, Gay Anne Granada; Tallo, Veronica; Lupisan, Socorro; Saito, Mayuko; Oshitani, Hitoshi

2016-06-27

Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

Respiratory viral diseases: access to RNA interference therapy

PubMed Central

Bitko, Vira; Barik, Sailen

2008-01-01

This review summarizes recent experimental achievements in the area of the development of new RNA interference (RNAi) therapeutics for the treatment of viral respiratory diseases. Delivery of siRNA to their intended target tissue remains the biggest problem for most therapeutic applications of these compounds. Appropriate formulations and chemical modifications for improved stability will boost the probability of utilization of RNAi drugs in the clinical applications. PMID:19081824

Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

PubMed

Kwak, Hyun Jung; Park, Dong Won; Kim, Jee Eun; Park, Min Kyung; Koo, Gun Woo; Park, Tai Sun; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Kim, Sang-Heon

2016-10-01

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants

PubMed Central

Espinosa, Yazmín; San Martín, Camila; Torres, Alejandro A.; Farfán, Mauricio J.; Torres, Juan P.; Avadhanula, Vasanthi; Piedra, Pedro A.; Tapia, Lorena I.

2017-01-01

The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies. PMID:28335547

Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

PubMed Central

Lawler, James; Paragas, Jason; Jahrling, Peter B.; Mollura, Daniel J.

2011-01-01

Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. PMID:21422476

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.

PubMed

Mazur, Natalie I; Bont, Louis; Cohen, Adam L; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A

2017-02-15

Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39-1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection. RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

PubMed

Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun

2017-04-01

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged <1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness <14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children

PubMed Central

Martin, Emily T.; Kuypers, Jane; Wald, Anna; Englund, Janet A.

2011-01-01

Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background  Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives  To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods  Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results  Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log10 copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions  Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to

[Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

PubMed

Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

2017-03-01

To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged <3 years, and there were more males than females. In the 275 HBoV-positive cases, 45 (16.36%) had single infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (P<0.05). The children with wheezing had a significantly higher viral load than those without wheezing (P<0.05). There was no significant difference in viral load between children with mild, moderate, and severe acute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon.

PubMed

Finianos, Mayda; Issa, Randi; Curran, Martin D; Afif, Claude; Rajab, Maryam; Irani, Jihad; Hakimeh, Noha; Naous, Amal; Hajj, Marie-Joelle; Hajj, Pierre; El Jisr, Tamima; El Chaar, Mira

2016-11-01

Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The diagnosis and management of respiratory viral infections in cystic fibrosis.

PubMed

Flight, William; Jones, Andrew

2017-03-01

Respiratory viruses, such as those that cause influenza and the common cold, are a regular feature of life for the entire human population. Among people with CF, these viruses are associated with prolonged respiratory illness and show a clear association with pulmonary exacerbations which in turn are associated with lung function decline and risk of death. Human rhinovirus is the most commonly encountered respiratory viral pathogen in CF although adenovirus, bocavirus, coronavirus, influenza, parainfluenza, metapneumovirus and respiratory syncytial virus are all also responsible for infections in this population. Areas covered: This article reviews the epidemiology, clinical impact and therapeutic options for respiratory virus infection in both children and adults with CF. Expert commentary: The management of CF to date has largely focused on airway clearance strategies, nutritional support and aggressive antibacterial therapy. We highlight the significant role that respiratory viruses play in CF lung disease and argue that these pathogens represent an under-exploited target in the battle to control patients' symptoms and disease progression.

Respiratory viral RNA on toys in pediatric office waiting rooms.

PubMed

Pappas, Diane E; Hendley, J Owen; Schwartz, Richard H

2010-02-01

Toys in pediatric office waiting rooms may be fomites for transmission of viruses. Eighteen samples were taken from office objects on 3 occasions. Samples were tested for presence of picornavirus (either rhinovirus or enterovirus) on all 3 sample days; in addition, January samples were tested for respiratory syncytial virus and March samples were tested for influenza A and B. In addition, 15 samples were obtained from the sick waiting room before and after cleaning. Polymerase chain reaction was used to detect picornavirus, respiratory syncytial virus, and influenza A or B virus. Finally, 20 samples were obtained from the fingers of a researcher after handling different toys in the sick waiting room, and samples were then obtained from all the same toys; all samples were tested for picornavirus by polymerase chain reaction. Viral RNA was detected on 11 of 52 (21%) of toys sampled. Ten of the positives were picornavirus; 1 was influenza B virus. Three (30%) of 10 toys from the new toy bag, 6 of 30 (20%) in the sick child waiting room, and 2 of 12 (17%) in the well child waiting room were positive. Six (40%) of 15 toys in the sick waiting room were positive for picornaviral RNA before cleaning; after cleaning, 4 (27%) of 15 were positive in spite of the fact that RNA was removed from 4 of 6 of the original positives. Three (15%) of 20 toys in the sick waiting room were positive for picornaviral RNA, but RNA was not transferred to the fingers of the investigator who handled these toys. About 20% of the objects in a pediatric office may be contaminated with respiratory viral RNA, most commonly picornavirus RNA. Cleaning with a disinfectant cloth was only modestly effective in removing the viral RNA from the surfaces of toys, but transfer of picornaviral RNA from toys to fingers was inefficient.

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

2010-01-01

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

PubMed Central

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

PubMed

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Bovine viral diarrhea virus: involvement in bovine respiratory disease and diagnostic challenges

USDA-ARS?s Scientific Manuscript database

This paper reviews the contribution of bovine viral diarrhea viruses (BVDV) to the development of Bovine Respiratory Disease (BRD). Veterinarians and producers generally consider BRD as one of the most significant diseases affecting production in the cattle industry. BRD can affect the performance (...

Respiratory viral infections in children with asthma: do they matter and can we prevent them?

PubMed Central

2012-01-01

Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children. PMID:22974166

Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development.

PubMed

Chonmaitree, Tasnee; Alvarez-Fernandez, Pedro; Jennings, Kristofer; Trujillo, Rocio; Marom, Tal; Loeffelholz, Michael J; Miller, Aaron L; McCormick, David P; Patel, Janak A; Pyles, Richard B

2015-01-01

Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.

PubMed

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons. At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study

PubMed Central

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Objective Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Study design Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. Results At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. Conclusion The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts. PMID:27309354

Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

PubMed

van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

2016-06-16

Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

Clinical Features of Respiratory Viral Infections Among Inpatients at a Major US Tertiary Care Hospital.

PubMed

Malhotra, Prashant; Luka, Arthur; McWilliams, Carla S; Poeth, Kaitlin G; Schwartz, Rebecca; Elfekey, Mohammed; Balwan, Sandy

2016-08-01

Respiratory viral illnesses (RVI) are reliably diagnosed by respiratory viral panel using polymerase chain reaction (RVP-PCR); however, owing to the scant data, clinical presentation alone is unreliable in establishing viral etiology. The primary objective of this study was to characterize signs and symptoms of RVI among inpatients in a major tertiary care hospital. Between 2013 and 2015, adult inpatients with RVI undergoing RVP-PCR were prospectively enrolled in our study. Clinical data were collected by interviews and electronic medical record reviews. Data analysis was performed using χ(2) testing, analysis of variance for continuous variables, and logistic regression modeling. Of 421 patients analyzed, 175 (41.7%) had a positive RVP-PCR. Patients were evenly matched at baseline except for renal disease. Multivariate logistic regression modeling demonstrated the following positive correlations: positive RVP-PCR with renal disease (odds ratio [OR] 2.08), cough (OR 2.28), and wheezing (OR 1.8); influenza with cough (OR 5.04), and renal disease (OR 2.17); metapneumovirus with age older than 65 (OR 3.24); respiratory syncytial viruses with wheezing (OR 3.42) and immunosuppression (OR 3.11); and parainfluenza with smoking (OR 3.16). Negative correlations included influenza with anosmia (OR 0.41); rhinovirus/enterovirus with feeling confined to bed (OR 0.3); metapneumovirus with smoking (OR 0.29); and parainfluenza with male sex (OR 0.22). In this descriptive study, we noted specific viral associations with clinical signs and symptoms among 421 inpatients with RVIs. With increasing RVP-PCR use, studies similar to ours may be able to better define the clinical presentation of RVIs and lead to evidence-based, clinical presentation-guided diagnostic and management algorithms.

Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

PubMed

Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

2015-11-01

Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

Microbiological and pathological examination of fatal calf pneumonia cases induced by bacterial and viral respiratory pathogens.

PubMed

Szeredi, Levente; Jánosi, Szilárd; Pálfi, Vilmos

2010-09-01

The infectious origin of fatal cases of calf pneumonia was studied in 48 calves from 27 different herds on postmortem examination. Lung tissue samples were examined by pathological, histological, bacterial culture, virus isolation and immunohistochemical methods for the detection of viral and bacterial infections. Pneumonia was diagnosed in 47/48 cases and infectious agents were found in 40/47 (85%) of those cases. The presence of multiple respiratory pathogens in 23/40 (57.5%) cases indicated the complex origin of fatal calf pneumonia. The most important respiratory pathogens were Mannheimia-Pasteurella in 36/40 (90%) cases, followed by Arcanobacterium pyogenes in 16/40 (40%) cases, Mycoplasma bovis in 12/40 (30%) cases, and bovine respiratory syncytial virus in 4/40 (10%) cases. Histophilus somni was detected in 2/40 (5%) cases, while bovine herpesvirus-1, bovine viral diarrhoea virus and parainfluenza virus-3 were each found in 1/40 (2.5%) case. Mastadenovirus, bovine coronavirus, influenza A virus or Chlamydiaceae were not detected.

Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

PubMed

Barik, Sailen

2009-01-01

Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

[Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing].

PubMed

Calvo, Cristina; Aguado, Isabel; García-García, María Luz; Ruiz-Chercoles, Esther; Díaz-Martinez, Eloisa; Albañil, Rosa María; Campelo, Olga; Olivas, Antonio; Muñóz-Gonzalez, Luisa; Pozo, Francisco; Fernandez-Arroyo, Rosa; Fernandez-Rincón, Adelaida; Calderon, Ana; Casas, Inmaculada

2017-08-01

It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P<.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P<.001 (OR: 2.18; 95% CI: 1.05-4.5). In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Viral etiology of respiratory infections in children under 5 years old living in tropical rural areas of Senegal: The EVIRA project.

PubMed

Niang, Mbayame Ndiaye; Diop, Ousmane M; Sarr, Fatoumata Diene; Goudiaby, Deborah; Malou-Sompy, Hubert; Ndiaye, Kader; Vabret, Astrid; Baril, Laurence

2010-05-01

Acute respiratory infection is one of the leading causes of child morbidity, especially in developing countries. Viruses are recognized as the predominant causative agents of acute respiratory infections. In Senegal, few data concerning the causes of respiratory infections are available, and those known relate mainly to classical influenza infections. Clinical and virological surveillance of acute respiratory infections was carried out in a rural community in children less than 5 years old. A standardized questionnaire was used and a nasopharyngeal swab sample was collected from each patient. These samples were tested for the detection of 20 respiratory viruses by multiplex RT-PCR or by viral culture. A total of 82 acute respiratory episodes were included, and 48 (58.5%) were found to be positive, with a total of 55 viral detections; several samples were positive for two (n = 5) or 3 (n = 1) viruses. Ten different viruses were identified: influenza viruses A, B, and C (n = 25), human respiratory syncytial virus type A (n = 13), rhinoviruses (n = 8), human coronaviruses type 229E and NL63 (n = 6), parainfluenza viruses 3 and 4 (n = 2), and bocavirus (n = 1). These results provide evidence on the importance and the diversity of viruses as causative agents of acute respiratory infections in children living in a rural community in Senegal. The establishment of sentinel surveillance sites could help estimate the burden of acute respiratory infection in the pediatric population and should help prepare the health care systems to identify and respond to new viral respiratory emergencies.

Impact of a viral respiratory epidemic on the practice of medicine and rehabilitation: severe acute respiratory syndrome.

PubMed

Lim, Peter A; Ng, Yee Sien; Tay, Boon Keng

2004-08-01

Severe acute respiratory syndrome (SARS) is a new respiratory viral epidemic that originated in China but has affected many parts of the world, with devastating impact on economies and the practice of medicine and rehabilitation. A novel coronavirus has been implicated, with transmission through respiratory droplets. Rehabilitation was significantly affected by SARS, because strict infection control measures run counter to principles such as multidisciplinary interactions, patients encouraging and learning from each other, and close physical contact during therapy. Immunocompromised patients who may silently carry SARS are common in rehabilitation and include those with renal failure, diabetes, and cancer. Routine procedures such as management of feces and respiratory secretions (eg, airway suctioning, tracheotomy care) have been classified as high risk. Personal protection equipment presented not only a physical but also a psychologic barrier to therapeutic human contact. Visitor restriction to decrease chances of disease transmission are particularly difficult for long-staying rehabilitation patients. At the height of the epidemic, curtailment of patient movement stopped all transfers for rehabilitation, and physiatrists had to function as general internists. Our experiences strongly suggest that rehabilitation institutions should have emergency preparedness plans because such epidemics may recur, whether as a result of nature or of bioterrorism.

Metagenomic Analysis of Respiratory Tract DNA Viral Communities in Cystic Fibrosis and Non-Cystic Fibrosis Individuals

PubMed Central

Haynes, Matthew; Schmieder, Robert; Angly, Florent E.; Silva, Joas; Tammadoni, Sassan; Nosrat, Bahador; Conrad, Douglas; Rohwer, Forest

2009-01-01

The human respiratory tract is constantly exposed to a wide variety of viruses, microbes and inorganic particulates from environmental air, water and food. Physical characteristics of inhaled particles and airway mucosal immunity determine which viruses and microbes will persist in the airways. Here we present the first metagenomic study of DNA viral communities in the airways of diseased and non-diseased individuals. We obtained sequences from sputum DNA viral communities in 5 individuals with cystic fibrosis (CF) and 5 individuals without the disease. Overall, diversity of viruses in the airways was low, with an average richness of 175 distinct viral genotypes. The majority of viral diversity was uncharacterized. CF phage communities were highly similar to each other, whereas Non-CF individuals had more distinct phage communities, which may reflect organisms in inhaled air. CF eukaryotic viral communities were dominated by a few viruses, including human herpesviruses and retroviruses. Functional metagenomics showed that all Non-CF viromes were similar, and that CF viromes were enriched in aromatic amino acid metabolism. The CF metagenomes occupied two different metabolic states, probably reflecting different disease states. There was one outlying CF virome which was characterized by an over-representation of Guanosine-5′-triphosphate,3′-diphosphate pyrophosphatase, an enzyme involved in the bacterial stringent response. Unique environments like the CF airway can drive functional adaptations, leading to shifts in metabolic profiles. These results have important clinical implications for CF, indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota. PMID:19816605

Rapid Multiplex PCR Assay To Identify Respiratory Viral Pathogens: Moving Forward Diagnosing The Common Cold

PubMed Central

Gordon, Sarah M; Elegino-Steffens, Diane U; Agee, Willie; Barnhill, Jason; Hsue, Gunther

2013-01-01

Upper respiratory tract infections (URIs) can be a serious burden to the healthcare system. The majority of URIs are viral in etiology, but definitive diagnosis can prove difficult due to frequently overlapping clinical presentations of viral and bacterial infections, and the variable sensitivity, and lengthy turn-around time of viral culture. We tested new automated nested multiplex PCR technology, the FilmArray® system, in the TAMC department of clinical investigations, to determine the feasibility of replacing the standard viral culture with a rapid turn-around system. We conducted a feasibility study using a single-blinded comparison study, comparing PCR results with archived viral culture results from a convenience sample of cryopreserved archived nasopharyngeal swabs from acutely ill ED patients who presented with complaints of URI symptoms. A total of 61 archived samples were processed. Viral culture had previously identified 31 positive specimens from these samples. The automated nested multiplex PCR detected 38 positive samples. In total, PCR was 94.5% concordant with the previously positive viral culture results. However, PCR was only 63.4% concordant with the negative viral culture results, owing to PCR detection of 11 additional viral pathogens not recovered on viral culture. The average time to process a sample was 75 minutes. We determined that an automated nested multiplex PCR is a feasible alternative to viral culture in an acute clinical setting. We were able to detect at least 94.5% as many viral pathogens as viral culture is able to identify, with a faster turn-around time. PMID:24052914

[Kagocel in the therapy of influenza and acute respiratory viral infections: Data analysis and systematization from the results of preclinical and clinical trials].

PubMed

Sologub, T V; Tsvetkov, V V

The article provides the summarized data of clinical trials evaluating the efficacy and safety of kagocel used to prevent and treat influenza and acute respiratory viral infections of different etiologies. The results of numerous preclinical and clinical trials suggest that the kagocel substance is highly safe and that it is appropriate to use the drug for the treatment and prevention of influenza and acute respiratory viral infections of another etiology.

Burden and viral aetiology of influenza-like illness and acute respiratory infection in intensive care units.

PubMed

Tramuto, Fabio; Maida, Carmelo Massimo; Napoli, Giuseppe; Mammina, Caterina; Casuccio, Alessandra; Cala', Cinzia; Amodio, Emanuele; Vitale, Francesco

2016-04-01

The purpose of this investigation was to study the viral aetiology of influenza-like illness (ILI) and acute respiratory tract infection (ARTI) among patients requiring intensive care unit admission. A cross-sectional retrospective study was carried out in Sicily over a 4-year period. A total of 233 respiratory samples of patients with ILI/ARTI admitted to intensive care units were molecularly analyzed for the detection of a comprehensive panel of aetiologic agents of viral respiratory infections. About 45% of patients was positive for at least one pathogen. Single aetiology occurred in 75.2% of infected patients, while polymicrobial infection was found in 24.8% of positive subjects. Influenza was the most common aetiologic agent (55.7%), especially among adults. Most of patients with multiple aetiology (76.9%) were adults and elderly. Mortality rates among patients with negative or positive aetiology did not significantly differ (52.4% and 47.6%, respectively). Highly transmissible respiratory pathogens are frequently detected among patients with ILI/ARTI admitted in intensive care units, showing the occurrence of concurrent infections by different viruses. The knowledge of the circulation of several types of microorganisms is of crucial importance in terms of appropriateness of therapies, but also for the implication in prevention strategies and hospital epidemiology. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

[Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age].

PubMed

Gil, Joana; Almeida, Sofia; Constant, Carolina; Pinto, Sara; Barreto, Rosário; Cristino, José Melo; Machado, Maria do Céu; Bandeira, Teresa

2018-03-01

Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. The study included 524 samples (451 patients); 448 (85,5%) had at least one virus identified. Viral coinfections were found in 159 (35,5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections.

PubMed

Self, Wesley H; Rosen, Jeffrey; Sharp, Stephan C; Filbin, Michael R; Hou, Peter C; Parekh, Amisha D; Kurz, Michael C; Shapiro, Nathan I

2017-10-07

C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59-93%), specificity of 93% (89-97%), positive predictive value (PPV) of 63% (45-79%), and a negative predictive value (NPV) of 97% (94-99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75-95%), specificity of 83% (76-89%), PPV of 64% (63-75%), and NPV of 95% (90-98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.

How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation

PubMed Central

Waghmare, Alpana; Englund, Janet A.

2016-01-01

The widespread use of multiplex molecular diagnostics has led to a significant increase in the detection of respiratory viruses in patients undergoing cytotoxic chemotherapy and hematopoietic cell transplantation (HCT). Respiratory viruses initially infect the upper respiratory tract and then progress to lower respiratory tract disease in a subset of patients. Lower respiratory tract disease can manifest itself as airflow obstruction or viral pneumonia, which can be fatal. Infection in HCT candidates may require delay of transplantation. The risk of progression differs between viruses and immunosuppressive regimens. Risk factors for progression and severity scores have been described, which may allow targeting treatment to high-risk patients. Ribavirin is the only antiviral treatment option for noninfluenza respiratory viruses; however, high-quality data demonstrating its efficacy and relative advantages of the aerosolized versus oral form are lacking. There are significant unmet needs, including data defining the virologic characteristics and clinical significance of human rhinoviruses, human coronaviruses, human metapneumovirus, and human bocavirus, as well as the need for new treatment and preventative options. PMID:26968533

Rapid viral diagnosis of acute respiratory infections: comparison of enzyme-linked immunosorbent assay and the immunofluorescence technique for detection of viral antigens in nasopharyngeal secretions.

PubMed Central

Grandien, M; Pettersson, C A; Gardner, P S; Linde, A; Stanton, A

1985-01-01

Nasopharyngeal secretions from adults and children were obtained in Stockholm, Sweden, for routine diagnosis of influenza A virus, influenza B virus, respiratory syncytial (RS) virus, parainfluenza type 3 virus, and adenovirus infections by demonstration of viral antigens directly in the specimens. The cells in nasopharyngeal secretions were pelleted by centrifugation for preparation of cell deposits for diagnosis by the immunofluorescence technique (IF) in London, England, and in Stockholm, whereas the supernatants were used to diagnose infection by the enzyme-linked immunosorbent assay (ELISA) in Stockholm. Titrations of the various purified viruses showed that ELISA could detect viral antigens in amounts corresponding to 1 to 10 ng of virus protein per test well. In a series of 73 specimens tested for influenza A, RS, and parainfluenza type 3 viruses by IF in London and by ELISA in Stockholm, 15 of 18 RS, 14 of 15 influenza A, and 2 of 2 parainfluenza type 3 viral infections were diagnosed by ELISA as compared with IF, giving sensitivities for RS and influenza A viral diagnosis of 83 and 93%, respectively, and a specificity of 100%. In another series of specimens from 35 patients tested for influenza B virus and adenovirus, five influenza B virus and four adenovirus infections were diagnosed by both methods; one additional influenza B infection was detected only by IF and another only by ELISA. Comparisons of diagnostic results between the two methods performed in Stockholm gave nonagreement of results for 37 of 1,593 tests (2.5%) for the five viruses. The conclusion reached was that the described ELISA, although a satisfactory test, had somewhat less sensitivity than did IF for the detection of respiratory viral infections. This could possibly be explained by unnecessary dilutions of specimens at the time of collection; transportation, processing, and storage of specimens were less complicated than for IF. PMID:2997270

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.

PubMed

Horton, Katherine C; Dueger, Erica L; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha

2017-01-01

Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is

Adenovirus type 4 respiratory infections with a concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees, a retrospective viral etiology study using next-generation sequencing.

PubMed

Hang, Jun; Vento, Todd J; Norby, Erica A; Jarman, Richard G; Keiser, Paul B; Kuschner, Robert A; Binn, Leonard N

2017-08-01

Human adenoviruses (HAdV), in particular types 4 and 7, frequently cause acute respiratory disease (ARD) during basic military training. HAdV4 and HAdV7 vaccines reduced the ARD risk in U.S. military. It is important to identify other respiratory pathogens and assess their potential impact on military readiness. In 2002, during a period when the HAdV vaccines were not available, throat swabs were taken from trainees (n = 184) with respiratory infections at Fort Jackson, South Carolina. Viral etiology was investigated initially with viral culture and neutralization assay and recently in this study by sequencing the viral isolates. Viral culture and neutralization assays identified 90 HAdV4 isolates and 27 additional cultures that showed viral cytopathic effects (CPE), including some with picornavirus-like CPE. Next-generation sequencing confirmed these results and determined viral genotypes, including 77 HAdV4, 4 HAdV3, 1 HAdV2, 17 coxsackievirus A21 (CAV21), and 1 enterovirus D68. Two samples were positive for both HAdV4 and CAV21. The identified genotypes are phylogenetically close to but distinct from those found during other years or in other military/non-military sites. HAdV4 is the predominant respiratory pathogen in unvaccinated military trainee. HAdV4 has temporal and demographic variability. CAV21 is a significant respiratory pathogen and needs to be evaluated for its current significance in military basic trainees. © 2017 Wiley Periodicals, Inc.

Acute metabolic responses to a combined viral-bacterial respiratory disease challenge in heifers administered transdermal flunixin meglumine

USDA-ARS?s Scientific Manuscript database

A trial was conducted to determine effects of altering time of transdermal flunixin meglumine (BTD; Banamine Transdermal, Merck Animal Health, Summit, NJ) administration relative to a viral-bacterial respiratory disease challenge in beef heifers. Thirty-two healthy heifers (170±21.1 kg BW) were assi...

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

PubMed

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK. A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort). The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007–2014

PubMed Central

Dueger, Erica L.; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha

2017-01-01

Introduction Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Methods Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1–3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. Results At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens–influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Conclusions Viral respiratory pathogens are common among SARI patients in the Eastern

Acute immunological responses to a combined viral-bacterial respiratory disease challenge in feedlot heifers supplemented with yeast

USDA-ARS?s Scientific Manuscript database

Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune responses to a combined viral-bacterial respiratory challenge. Thirty-two beef heifers (325 +/- 19.2 kg BW) were selected and randomly assigned to one of two treatments, and fed for 3...

Zinc source and concentration altered physiological responses of beef heifers during a combined viral-bacterial respiratory challenge

USDA-ARS?s Scientific Manuscript database

Three treatments were evaluated in feedlot heifers to determine the effects of zinc supplementation on the immune response to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (255+/-15 kg) were subjected to a 30d period of Zn depletion, then randomly assigned to one ...

Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

PubMed

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2016-01-01

Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.

Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

PubMed Central

Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

2016-01-01

Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

MicroRNA-like viral small RNA from porcine reproductive and respiratory syndrome virus negatively regulates viral replication by targeting the viral nonstructural protein 2.

PubMed

Li, Na; Yan, Yunhuan; Zhang, Angke; Gao, Jiming; Zhang, Chong; Wang, Xue; Hou, Gaopeng; Zhang, Gaiping; Jia, Jinbu; Zhou, En-Min; Xiao, Shuqi

2016-12-13

Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification. Of these, the structures with the lowest minimum free energy (MFE) values predicted for PRRSV-vsRNA1 corresponded to typical stem-loop, hairpin structures. Inhibition of PRRSV-vsRNA1 function led to significant increases in viral replication. Transfection with PRRSV-vsRNA1 mimics significantly inhibited PRRSV replication in primary porcine alveolar macrophages (PAMs). The time-dependent increase in the abundance of PRRSV-vsRNA1 mirrored the gradual upregulation of PRRSV RNA expression. Knockdown of proteins associated with cellular miRNA biogenesis demonstrated that Drosha and Argonaute (Ago2) are involved in PRRSV-vsRNA1 biogenesis. Moreover, PRRSV-vsRNA1 bound specifically to the nonstructural protein 2 (NSP2)-coding sequence of PRRSV genome RNA. Collectively, the results reveal that PRRSV encodes a functional PRRSV-vsRNA1 which auto-regulates PRRSV replication by directly targeting and suppressing viral NSP2 gene expression. These findings not only provide new insights into the mechanism of the pathogenesis of PRRSV, but also explore a potential avenue for controlling PRRSV infection using viral small RNAs.

Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room

PubMed Central

Silva, Denise R; Viana, Vinícius P; Müller, Alice M; Livi, Fernando P; Dalcin, Paulo de Tarso R

2014-01-01

Background Respiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections. Objectives The objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010. Methods Eleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis. Results Influenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant. Conclusions At least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI. PMID:24034701

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

PubMed Central

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

Cost burden of viral respiratory infections: issues for formulary decision makers.

PubMed

Bertino, Joseph S

2002-04-22

Viral respiratory infections (VRIs) are a common malady associated with considerable costs in terms of decreased productivity and time lost from work or school, visits to health-care providers, and the amount of drugs prescribed. Both total respiratory illness and rhinovirus infection peak during the fall and spring seasons, although the average percentage of office visits by patients with a rhinovirus infection is moderately high throughout the year. Most common cold remedies are relatively ineffective and may produce side effects that contribute to increased health-care costs. Antibiotic therapy is widely overused and misused despite evidence that antibiotics fail to treat the cause of VRI or prevent secondary bacterial infections. Increasing use of antibiotics has a significant impact on health-care costs and the emergence of antimicrobial resistance. Reasons for overprescribing antibiotics are varied, but they often involve physician and patient attitudes and expectations. Although treatment of VRIs poses challenges for effective formulary management, several steps can be taken to facilitate the introduction of antiviral agents, including patient and provider education, the development of rapid diagnostic tests, and medical-economics studies to determine the true cost of antiviral therapy.

Spatial and Temporal Spread of Acute Viral Respiratory Infections in Young Children Living in High-Altitude Rural Communities: A Prospective Household-Based Study

PubMed Central

Cherry, Charlotte Buehler; Griffin, Marie R.; Edwards, Kathryn M.; Williams, John V.; Gil, Ana I.; Verastegui, Hector; Lanata, Claudio F.; Grijalva, Carlos G

2016-01-01

Background Few studies have described patterns of transmission of viral acute respiratory infections (ARI) in children in developing countries. We examined the spatial and temporal spread of viral ARI among young children in rural Peruvian highland communities. Previous work has described intense social interactions in those communities, which could influence the transmission of viral infections. Methods We enrolled and followed children <3 years of age for detection of ARI during the 2009–2011 respiratory seasons in a rural setting with relatively wide geographic dispersion of households and communities. Viruses detected included influenza, respiratory syncytial virus (RSV), human metapneumovirus (MPV), and parainfluenza 2 and 3 viruses (PIV2; PIV3). We used geospatial analyses to identify specific viral infection hot spots with high ARI incidence. We also explored the local spread of ARI from index cases using standard deviational ellipses. Results Geospatial analyses revealed hot spots of high ARI incidence around the index cases of influenza outbreaks and RSV outbreak in 2010. Although PIV3 in 2009 and PIV2 in 2010 showed distinct spatial hot spots, clustering was not in proximity to their respective index cases. No significant aggregation around index cases was noted for other viruses. Standard deviational ellipse analyses suggested that influenza B and RSV in 2010, and MPV in 2011 spread temporally in alignment with the major road network. Conclusions Despite the geographic dispersion of communities in this rural setting, we observed a rapid spread of viral ARI among young children. Influenza strains and RSV in 2010 had distinctive outbreaks arising from their index cases. PMID:27404599

Viral and Mycoplasma pneumoniae pneumonias in school-age children: three-year follow-up of respiratory function.

PubMed

Todisco, T; de Benedictis, F M; Dottorini, M

1989-01-01

We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.

Severity of viral coinfection in hospitalized infants with respiratory syncytial virus infection.

PubMed

De Paulis, Milena; Gilio, Alfredo Elias; Ferraro, Alexandre Archanjo; Ferronato, Angela Esposito; do Sacramento, Patrícia Rossi; Botosso, Viviane Fongaro; Oliveira, Danielle Bruna Leal de; Marinheiro, Juliana Cristina; Hársi, Charlotte Marianna; Durigon, Edison Luiz; Vieira, Sandra Elisabete

2011-01-01

To compare the severity of single respiratory syncytial virus (RSV) infections with that of coinfections. A historical cohort was studied, including hospitalized infants with acute RSV infection. Nasopharyngeal aspirate samples were collected from all patients to detect eight respiratory viruses using molecular biology techniques. The following outcomes were analyzed: duration of hospitalization and of oxygen therapy, intensive care unit admission and need of mechanical ventilation. Results were adjusted for confounding factors (prematurity, age and breastfeeding). A hundred and seventy six infants with bronchiolitis and/or pneumonia were included in the study. Their median age was 4.5 months. A hundred and twenty one had single RSV infection and 55 had coinfections (24 RSV + adenovirus, 16 RSV + human metapneumovirus and 15 other less frequent viral associations). The four severity outcomes under study were similar in the group with single RSV infection and in the coinfection groups, independently of what virus was associated with RSV. Virus coinfections do not seem to affect the prognosis of hospitalized infants with acute RSV infection.

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

Yeast supplementation reduced the immune and metabolic responses to a combined viral-bacterial respiratory disease challenge in feedlot heifers

USDA-ARS?s Scientific Manuscript database

Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune and metabolic responses to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (324 ± 19.2 kg BW) were selected and randomly assigned to one of two treat...

Viral bronchiolitis.

PubMed

Florin, Todd A; Plint, Amy C; Zorc, Joseph J

2017-01-14

Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Respiratory syncytial virus and influenza are the key viral pathogens in children <2 years hospitalized with bronchiolitis and pneumonia in Islamabad Pakistan.

PubMed

Bashir, Uzma; Nisar, Nadia; Arshad, Yasir; Alam, Muhammad Masroor; Ashraf, Asiya; Sadia, Hajra; Kazi, Birjees Mazher; Zaidi, Syed Sohail Zahoor

2017-03-01

Pneumonia remains a leading cause of morbidity and mortality in developing countries. Comprehensive surveillance data are needed to review the prevention and control strategies. We conducted active surveillance of acute lower respiratory infections among children aged <2 years hospitalized at two hospitals of Islamabad, Pakistan. Viral etiology was determined using real-time PCR on respiratory specimens collected during March 2011-April 2012. The overall mean age was 7.83 ± 5.25 months while no statistical difference between age or sex distribution of patients with positive and negative viral etiology (p > 0.05). The average weight of the study group was 6.1 ± 2.25 kg. ≥1 viral pathogens were detected in 75% cases. Major respiratory viruses included RSV-A: 44%, RSV-B: 23%, Influenza-A: 24.5%, Influenza-B: 7%, Adenovirus: 8.4% and HmPV: 5.2%. A single, dual or multiple viral pathogens were detected in 43%, 27% and 5.2% patients respectively. Common symptoms were cough (95%), apnoea (84%), fever (78%), wheeze (64.5%), nasal congestion (55%) and rhinorrhea (48%). Among the RSV positive cases, 2-6 months age group had highest detection rate for RSV-A (30%, n = 21/69) and RSV-B (20%, n = 14/69) while patients infected with Influenza-A were in 2.1-6 months age group (61%, 23/38). Statistically significant difference was observed between RSV-positive and negative cases for nutrition status (p = 0.001), cigarette/wood smoke exposure (p = 0.001) and concomitant clinical findings. Most patients had successful outcome on combination therapy with bronchodilators, inhaled steroids and antibiotics. Our findings underscore high burden of ALRI in Pakistan. Interventions targeting viral pathogens coupled with improved diagnostic approaches are critical for better prevention and control.

Bovine viral diarrhea virus (BVDV) 1b: predominant BVDV subtype in calves with respiratory disease

PubMed Central

Fulton, Robert W.; Ridpath, Julia F.; Saliki, Jeremiah T.; Briggs, Robert E.; Confer, Anthony W.; Burge, Lurinda J.; Purdy, C. W.; Loan, Raymond W.; Duff, Glenn C.; Payton, Mark E.

2002-01-01

The prevalence of bovine viral diarrhea virus (BVDV) infections was determined in 2 groups of stocker calves with acute respiratory disease. Both studies used calves assembled after purchase from auction markets by an order buyer and transported to feedyards, where they were held for approximately 30 d. In 1 study, the calves were mixed with fresh ranch calves from a single ranch. During the studies, at day 0 and at weekly intervals, blood was collected for viral antibody testing and virus isolation from peripheral blood leukocytes (PBLs), and nasal swabs were taken for virus isolation. Samples from sick calves were also collected. Serum was tested for antibodies to bovine herpesvirus-1 (BHV-1), BVDV1a, 1b, and 2, parainfluenza 3 virus (PI3V), and bovine respiratory syncytial virus (BRSV). The lungs from the calves that died during the studies were examined histopathologically, and viral and bacterial isolation was performed on lung homogenates. BVDV was isolated from calves in both studies; the predominant biotype was noncytopathic (NCP). Differential polymerase chain reaction (PCR) and nucleic acid sequencing showed the predominant subtype to be BVDV1b in both studies. In 1999, NCP BVDV1b was detected in numerous samples over time from 1 persistently infected calf; the calf did not seroconvert to BVDV1a or BVDV2. In both studies, BVDV was isolated from the serum, PBLs, and nasal swabs of the calves, and in the 1999 study, it was isolated from lung tissue at necropsy. BVDV was demonstrated serologically and by virus isolation to be a contributing factor in respiratory disease. It was isolated more frequently from sick calves than healthy calves, by both pen and total number of calves. BVDV1a and BVDV2 seroconversions were related to sickness in selected pens and total number of calves. In the 1999 study, BVDV-infected calves were treated longer than noninfected calves (5.643 vs 4.639 d; P = 0.0902). There was a limited number of BVDV1a isolates and, with BVDV1b

Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

PubMed

Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

2018-05-01

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P < 0.001). The viral mean load was 4.81 ± 1.98 log10 copies/1000 cells for patients under the age of 4-year-old (P < 0.001). The viral mean loads were 4.51 ± 2.04 cells in patients with low respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease

PubMed Central

Kim, Edy Y.; Battaile, John T.; Patel, Anand C.; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H.; Benoit, Loralyn A.; Byers, Derek E.; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W.; Morton, Jeffrey D.; Castro, Mario; Polineni, Deepika; Patterson, G. Alexander; Schwendener, Reto A.; Allard, John D.; Peltz, Gary; Holtzman, Michael J.

2008-01-01

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of a chronic lung disease that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after infection with a common type of respiratory virus is cleared to trace levels of noninfectious virus. Unexpectedly, the chronic inflammatory disease arises independently of an adaptive immune response and is driven by IL-13 produced by macrophages stimulated by CD1d-dependent TCR-invariant NKT cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a novel NKT cell-macrophage innate immune axis. PMID:18488036

Middle East Respiratory Syndrome (MERS)

MedlinePlus

... Controls Cancel Submit Search The CDC Middle East Respiratory Syndrome (MERS) Note: Javascript is disabled or is ... Recommend on Facebook Tweet Share Compartir Middle East Respiratory Syndrome (MERS) is viral respiratory illness that was ...

Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.

PubMed

Connors, Thomas J; Baird, J Scott; Yopes, Margot C; Zens, Kyra D; Pethe, Kalpana; Ravindranath, Thyyar M; Ho, Siu-Hong; Farber, Donna L

2018-05-30

Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8 + T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA + T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA + T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages. Copyright © 2018 by The American Association of Immunologists, Inc.

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

PubMed

Santolaya, M E; Alvarez, A M; Acuña, M; Avilés, C L; Salgado, C; Tordecilla, J; Varas, M; Venegas, M; Villarroel, M; Zubieta, M; Toso, A; Bataszew, A; Farfán, M J; de la Maza, V; Vergara, A; Valenzuela, R; Torres, J P

2017-03-01

To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

PubMed Central

Feldman, Amy S.; He, Yuan; Moore, Martin L.; Hershenson, Marc B.

2015-01-01

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts. PMID:25369458

Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

PubMed

Grissett, G P; White, B J; Larson, R L

2015-01-01

Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.

PubMed

Aglipay, Mary; Birken, Catherine S; Parkin, Patricia C; Loeb, Mark B; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S; Mazzulli, Tony; Maguire, Jonathon L

2017-07-18

Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice-based research network in Toronto, Ontario, Canada. Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, -0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

PubMed Central

Mei, Minghua; Mehta, Reena

2017-01-01

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness. PMID:28267794

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

PubMed

Piedra, Felipe-Andrés; Mei, Minghua; Avadhanula, Vasanthi; Mehta, Reena; Aideyan, Letisha; Garofalo, Roberto P; Piedra, Pedro A

2017-01-01

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.

Quantitative interactome reveals that porcine reproductive and respiratory syndrome virus nonstructural protein 2 forms a complex with viral nucleocapsid protein and cellular vimentin.

PubMed

Song, Tao; Fang, Liurong; Wang, Dang; Zhang, Ruoxi; Zeng, Songlin; An, Kang; Chen, Huanchun; Xiao, Shaobo

2016-06-16

Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has heavily impacted the global swine industry. The PRRSV nonstructural protein 2 (nsp2) plays crucial roles in viral replication and host immune regulation, most likely by interacting with viral or cellular proteins that have not yet been identified. In this study, a quantitative interactome approach based on immunoprecipitation and stable isotope labeling with amino acids in cell culture (SILAC) was performed to identify nsp2-interacting proteins in PRRSV-infected cells with an nsp2-specific monoclonal antibody. Nine viral proteins and 62 cellular proteins were identified as potential nsp2-interacting partners. Our data demonstrate that the PRRSV nsp1α, nsp1β, and nucleocapsid proteins all interact directly with nsp2. Nsp2-interacting cellular proteins were classified into different functional groups and an interactome network of nsp2 was generated. Interestingly, cellular vimentin, a known receptor for PRRSV, forms a complex with nsp2 by using viral nucleocapsid protein as an intermediate. Taken together, the nsp2 interactome under the condition of virus infection clarifies a role of nsp2 in PRRSV replication and immune evasion. Viral proteins must interact with other virus-encoded proteins and/or host cellular proteins to function, and interactome analysis is an ideal approach for identifying such interacting proteins. In this study, we used the quantitative interactome methodology to identify the viral and cellular proteins that potentially interact with the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) under virus infection conditions, thus providing a rich source of potential viral and cellular interaction partners for PRRSV nsp2. Based on the interactome data, we further demonstrated that PRRSV nsp2 and nucleocapsid protein together with cellular vimentin, form a complex that may be essential for viral attachment and

Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity

PubMed Central

Bryant, Juliet E.; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; van Doorn, H. Rogier

2016-01-01

Background Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. Methods A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. Results Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. Conclusion We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity. PMID:27500954

Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil.

PubMed

Gurgel, Ricardo Queiroz; Bezerra, Patrícia Gomes de Matos; Duarte, Maria do Carmo Menezes Bezerra; Moura, Adriana Ávila; Souza, Edna Lucia; Silva, Luciana Sobral da Silveira; Suzuki, Claudia Eiko; Peixoto, Rodrigo Buzzatti

2016-04-01

Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

PubMed Central

Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.

2017-01-01

Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein.

PubMed

Souza, Priscila Silva Sampaio; Barbosa, Lia Vezenfard; Diniz, Larissa Figueiredo Alves; da Silva, Gabriel Soares; Lopes, Bruno Rafael Pereira; Souza, Pedro Miyadaira Ribeiro; de Araujo, Gabriela Campos; Pessoa, Diogo; de Oliveira, Juliana; Souza, Fátima Pereira; Toledo, Karina Alves

2018-06-02

Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract, and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. The airways of patients infected with hRSV exhibit intense neutrophil infiltration, which is responsible for the release of neutrophil extracellular traps (NETs). These are extracellular structures consisting of DNA associated with intracellular proteins, and are efficient in capturing and eliminating various microorganisms, including some viruses. hRSV induces the release of NETs into the lung tissue of infected individuals; however, the pathophysiological consequences of this event have not been elucidated. The objective of this study was to utilize in vitro and in silico assays to investigate the impact of NETs on hRSV infection. NETs, generated by neutrophils stimulated with phorbol myristate acetate (PMA), displayed long fragments of DNA and an electrophoretic profile suggestive of the presence of proteins that are classically associated with these structures (elastase, cathepsin G, myeloperoxidase, and histones). The presence of NETs (>2 μg/ml) in HEp-2 cell culture medium resulted in cellular cytotoxicity of less than 50%. Pre-incubation (1 h) of viral particles (multiplicity of infection (MOI) values of 0.1, 0.5, and 1.0) with NETs (2-32 μg/ml) resulted in cellular protection from virus-induced death of HEp-2 cells. Concurrently, there was a reduction in the formation of syncytia, which is related to decreased viral spread in infected tissue. Results from western blotting and molecular docking, suggest interactions between F protein of the hRSV viral envelope and BPI (bactericidal permeability-increasing protein), a microbicidal member of NETs. Interactions occurred at sites important for the neutralization and coordination of the hRSV infection/replication process. Our results

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

PubMed Central

Aglipay, Mary; Birken, Catherine S.; Parkin, Patricia C.; Loeb, Mark B.; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S.; Mazzulli, Tony

2017-01-01

Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. Objective To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. Design, Setting, and Participants A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada. Interventions Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Results Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was

Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia.

PubMed

Hakim, Hana; Dallas, Ronald; Zhou, Yinmei; Pei, Dequing; Cheng, Cheng; Flynn, Patricia M; Pui, Ching-Hon; Jeha, Sima

2016-03-01

Knowledge regarding the incidence, clinical course, and impact of respiratory viral infections in children with acute lymphoblastic leukemia (ALL) is limited. A retrospective cohort of patients with newly diagnosed ALL who were treated on the Total Therapy XVI protocol at St Jude Children's Research Hospital between 2007 and 2011 was evaluated. Of 223 children, 95 (43%) developed 133 episodes of viral acute respiratory illness (ARI) (incidence, 1.1 per 1000 patient-days). ARI without viral etiology was identified in 65 patients (29%) and no ARI was detected in 63 patients (28%). There were no significant associations noted between race, sex, age, or ALL risk group and the development of ARI. Children receiving induction chemotherapy were found to be at the highest risk of viral ARI (incidence, 2.3 per 1000 patient-days). Influenza virus was the most common virus (38%) followed by respiratory syncytial virus (33%). Of 133 episodes of viral ARI, 61% of patients were hospitalized, 26% experienced a complicated course, 80% had their chemotherapy delayed, and 0.7% of patients died. Twenty-four patients (18%) developed viral lower respiratory tract infections (LRTI), 5 of whom (21%) had complications. Patients with viral LRTI had a significantly lower nadir absolute lymphocyte count; were sicker at the time of presentation; and were more likely to have respiratory syncytial virus, to be hospitalized, and to have their chemotherapy delayed for longer compared with those with viral upper respiratory tract infections. Despite the low incidence of viral ARI in children with ALL, the associated morbidity, mortality, and delay in chemotherapy remain clinically significant. Viral LRTI was especially associated with high morbidity requiring intensive care-level support. Cancer 2016;122:798-805. © 2015 American Cancer Society. © 2015 American Cancer Society.

Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness.

PubMed

Miller, E Kathryn; Williams, John V; Gebretsadik, Tebeb; Carroll, Kecia N; Dupont, William D; Mohamed, Yassir A; Morin, Laura-Lee; Heil, Luke; Minton, Patricia A; Woodward, Kimberly; Liu, Zhouwen; Hartert, Tina V

2011-04-01

Risk factors for severe human rhinovirus (HRV)-associated infant illness are unknown. We sought to examine the role of HRV infection in infant respiratory tract illness and assess viral and host risk factors for HRV-associated disease severity. We used a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory tract illness during the fall-spring months of 2004-2008. Illness severity was determined by using an ordinal bronchiolitis severity score, with higher scores indicating more severe disease. HRV was identified by means of real-time RT-PCR. The VP4/VP2 region from HRV-positive specimens was sequenced to determine species. Of 630 infants with bronchiolitis or upper respiratory tract illnesses (URIs), 162 (26%) had HRV infection; HRV infection was associated with 18% of cases of bronchiolitis and 47% of cases of URI. Among infants with HRV infection, 104 (64%) had HRV infection alone. Host factors associated with more severe HRV-associated illness included a maternal and family history of atopy (median score of 3.5 [interquartile range [IQR], 1.0-7.8] vs 2.0 [IQR, 1.0-5.2] and 3.5 [IQR, 1.0-7.5] vs 2.0 [IQR, 0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in the risk for more severe HRV-associated bronchiolitis (odds ratio, 2.39; 95% CI, 1.14-4.99; P = .02). In a similar model maternal asthma was also associated with greater HRV-associated bronchiolitis severity (odds ratio, 2.49, 95% CI, 1.10-5.67; P = .03). Among patients with HRV infection, 35% had HRVA, 6% had HRVB, and 30% had HRVC. HRV infection was a frequent cause of bronchiolitis and URIs among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial viral genetic diversity was seen among the patients with HRV infection, and predominant groups varied by season and year. Host factors, including maternal atopy, were associated with more severe

Viral infections in transplant recipients.

PubMed

Razonable, R R; Eid, A J

2009-12-01

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

[Immunomodulators in Therapy of Respiratory Infections].

PubMed

Isakov, V A; Isakov, D V

2014-01-01

Viral infections provoke dysbalance in the interferon system and inhibition of the cellular and phagocytic responses of the host. Long-term persistence of pathogenic viruses and bacteria induce atopy and could aggravate chronic respiratory diseases. The up-to-date classification of immunomodulators is described. High efficacy of interferon inductors, such as cycloferon and some others as auxiliary means in therapy or prophylaxis (immunorehabilitation) of viral respiratory infections in adults and children was shown.

Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

PubMed Central

Bitko, Vira; Oldenburg, Anja; Garmon, Nicolle E; Barik, Sailen

2003-01-01

Background Actin is required for the gene expression and morphogenesis of respiratory syncytial virus (RSV), a clinically important Pneumovirus of the Paramyxoviridae family. In HEp-2 cells, RSV infection also induces actin stress fibers, which may be important in the immunopathology of the RSV disease. Profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. Thus, we tested the role of profilin in RSV growth and RSV-actin interactions in cultured cells (ex vivo). Results We tested three cell lines: HEp-2 (human), A549 (human), and L2 (rat). In all three, RSV grew well and produced fused cells (syncytium), and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers. Conclusions Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin. PMID:12740026

Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample.

PubMed

Clark, Tristan W; Medina, Marie-jo; Batham, Sally; Curran, Martin D; Parmar, Surendra; Nicholson, Karl G

2014-11-01

Many adult patients hospitalised with acute respiratory illness have viruses detected but the overall importance of viral infection compared to bacterial infection is unclear. Patients were recruited from two acute hospital sites in Leicester (UK) over 3 successive winters. Samples were taken for viral and bacterial testing. Of the 780 patients hospitalised with acute respiratory illness 345 (44%) had a respiratory virus detected. Picornaviruses were the most commonly isolated viruses (detected in 23% of all patients). Virus detection rates exceeded 50% in patients with exacerbation of asthma (58%), acute bronchitis and Influenza-like-illness (64%), and ranged from 30 to 50% in patients with an exacerbation of COPD (38%), community acquired pneumonia (36%) and congestive cardiac failure (31%). Bacterial detection was relatively frequent in patients with exacerbation of COPD and pneumonia (25% and 33% respectively) but was uncommon in all other groups. Antibiotic use was high across all clinical groups (76% overall) and only 21% of all antibiotic use occurred in patients with detectable bacteria. Respiratory viruses are the predominant detectable aetiological agents in most hospitalised adults with acute respiratory illness. Antibiotic usage in hospital remains excessive including in clinical conditions associated with low rates of bacterial detection. Efforts at reducing excess antibiotic use should focus on these groups as a priority. Registered International Standard Controlled Trial Number: 21521552. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

PubMed Central

Martínez, Isidoro; Oliveros, Juan C.; Cuesta, Isabel; de la Barrera, Jorge; Ausina, Vicente; Casals, Cristina; de Lorenzo, Alba; García, Ernesto; García-Fojeda, Belén; Garmendia, Junkal; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortín, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos-Sevillano, Elisa; Regueiro, Verónica; Rodriguez-Frandsen, Ariel; Solís, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.

2017-01-01

Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here. PMID:28298903

Development of Internal Controls for the Luminex Instrument as Part of a Multiplex Seven-Analyte Viral Respiratory Antibody Profile

PubMed Central

Martins, Thomas B.

2002-01-01

The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument’s ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument’s multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay. PMID:11777827

Development of internal controls for the Luminex instrument as part of a multiplex seven-analyte viral respiratory antibody profile.

PubMed

Martins, Thomas B

2002-01-01

The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument's ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument's multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay.

The impact of cell regeneration on the dynamics of viral coinfection

NASA Astrophysics Data System (ADS)

Pinky, Lubna; Dobrovolny, Hana M.

2017-06-01

Many mathematical models of respiratory viral infections do not include regeneration of cells within the respiratory tract, arguing that the infection is resolved before there is significant cellular regeneration. However, recent studies have found that ˜40% of patients hospitalized with influenza-like illness are infected with at least two different viruses, which could potentially lead to longer-lasting infections. In these longer infections, cell regeneration might affect the infection dynamics, in particular, allowing for the possibility of chronic coinfections. Several mathematical models have been used to describe cell regeneration in infection models, though the effect of model choice on the predicted time course of viral coinfections is not clear. We investigate four mathematical models incorporating different mechanisms of cell regeneration during respiratory viral coinfection to determine the effect of cell regeneration on infection dynamics. We perform linear stability analysis for each of the models and find the steady states analytically. The analysis suggests that chronic illness is possible but only with one viral species; chronic coexistence of two different viral species is not possible with the regeneration models considered here.

Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

PubMed

Vakil, Erik; Evans, Scott E

2017-03-01

Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Respiratory infections in elderly people: Viral role in a resident population of elderly care centers in Lisbon, winter 2013-2014.

PubMed

Chasqueira, Maria-Jesus; Paixão, Paulo; Rodrigues, Maria-Lúcia; Piedade, Cátia; Caires, Iolanda; Palmeiro, Teresa; Botelho, Maria-Amalia; Santos, Madalena; Curran, Martin; Guiomar, Raquel; Pechirra, Pedro; Costa, Inês; Papoila, Ana; Alves, Marta; Neuparth, Nuno

2018-04-01

The aim of this study was to analyze the etiology and clinical consequences of viral respiratory infections in 18 elderly care centers (ECC) in Lisbon, which housed a total of 1022 residents. Nasopharyngeal swabs were collected whenever an elderly had symptoms of acute respiratory infections (ARI). PCR and RT-PCR were performed for influenza A/B, human parainfluenza virus 1-4, adenovirus, human metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus, enterovirus, human coronavirus and human Bocavirus (HBoV). Array cards for atypical bacteria were also used in severe cases. In total, 188 episodes of ARI were reported, being rhinovirus the most frequently detected (n=53), followed by influenza A(H3) (n=19) and HBoV (n=14). Severe infections were reported in 19 patients, 11 of which were fatal, Legionela pneumophila, rhinovirus, HMPV and RSV associated with these fatalities. Nine influenza strains were analyzed, all antigenically dissimilar from vaccine strain 2013/14. "Age", "HMPV" and "Respiratory disease" showed an association with severe infection. In this study an etiologic agent could be found in 60% of the acute respiratory episodes. These data provides information about the circulating viruses in ECC and highlights the importance of searching both viruses and atypical bacteria in severe ARI. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

PubMed Central

Bergström, Tomas; Kann, Nina; Adamiak, Beata; Hannoun, Charles; Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen; Kint, Joeri; Forlenza, Maria; Müller, Marcel A.; Drosten, Christian; Thiel, Volker; Trybala, Edward

2014-01-01

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. PMID:24874215

Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs

PubMed Central

England, Matthew R.; Jurcic Smith, Kristen L.; He, Taojun; Wijetunge, Dona Saumya; Chamberland, Robin R.; Menegus, Marilyn; Swierkosz, Ella M.; Jerris, Robert C.; Greene, Wallace

2017-01-01

ABSTRACT The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens. PMID:29212701

Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP).

PubMed

Kim, Eun Sun; Park, Kyoung Un; Lee, Sang Hoon; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek; Lee, Jae Ho

2018-01-01

Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral-bacterial coinfection and bacterial infection, and the CAP group showed similar results. The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral-bacterial coinfection or bacterial infection.

The role of respiratory viruses in the etiology of bacterial pneumonia

PubMed Central

Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy

2016-01-01

Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. PMID:26884414

[THE COMPARATIVE ANALYSIS OF EFFECTIVENESS OF QUICK TESTS IN DIAGNOSTIC OF INFLUENZA AND RESPIRATORY SYNCYTIAL VIRAL INFECTION IN CHILDREN].

PubMed

Petrova, E R; Sukhovetskaia, V P; Pisareva, M M; Maiorova, V G; Sverlova, M V; Danilenko, D M; Petrova, P A; Krivitskaia, V Z; Sominina, A A

2015-11-01

The analysis was implemented concerning diagnostic parameters of commercial quick tests (immune chromatographic tests BinaxNOW Influenza A&B and BinaxNow RSV Alere, Scarborough Inc., USA) under detection of antigens of influenza virus A and respiratory syncytial virus in clinical materials. The polymerase chain reaction in real-time and isolation ofviruses in cell cultures. The analysis of naso-pharyngeal smears from 116 children demonstrated that sensitivity and specifcity of detection of influenza virus A using device mariPOC in comparison with polymerase chain reaction made up to 93.8% and 99.0% correspondingly at total concordance of results of both techniques as 98.3%. At diagnosing of respiratory syncytial virus using device mariPOC parameters made up to 77.3%, 98.9% and 862% as compared with polymerase chain reaction. The sensitivity, specificity and total concordance of results of immune chromatographic tests BinaxNOW in comparison ofpolymerase chain reaction made up to 86.7%, 100% and 96.2% correspondingly at detection of influenza virus A and 80.9%, 97.4% and 91.6% correspondingly at detection of respiratory syncytial virus. In comparison with isolation technique in cell cultures sensitivity of system mariPOC and immune chromatographic tests proved to be in 1.3-1.4 times higher at detection of influenza virus A and in 1.7-2 times higher in case of isolation of respiratory syncytial virus. There is no statistically significant differences between diagnostic parameters received for mariPOC and immune chromatographic tests at diagnosing influenza virus A and respiratory syncytial viral infection.

Bovine Respiratory Disease: Sex matters

USDA-ARS?s Scientific Manuscript database

To evaluate a potential sexual dimorphic innate immune response to respiratory disease, 8 steers and 7 heifers (BW=280±4 kg) were subjected to a combined viral-bacterial respiratory disease challenge utilizing BHV-1 (intranasal; 1.0x10^8 PFU/mL/nostril) at -72h and Mannheimia haemolytica (MH; intrat...

Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menachery, Vineet D.; Gralinski, Lisa E.; Mitchell, Hugh D.

ABSTRACT Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2'O-MTase activity had only a marginal impactmore » on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures andin vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2'O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCECoronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2'O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN

Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

PubMed Central

Menachery, Vineet D.; Gralinski, Lisa E.; Mitchell, Hugh D.; Dinnon, Kenneth H.; Leist, Sarah R.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Stratton, Kelly G.; Cockrell, Adam S.; Debbink, Kari; Sims, Amy C.; Waters, Katrina M.

2017-01-01

ABSTRACT Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2′O-methyltransferase (2′O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2′O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCE Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN

Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city

PubMed Central

Bhuyan, Golam Sarower; Hossain, Mohammad Amir; Sarker, Suprovath Kumar; Rahat, Asifuzzaman; Islam, Md Tarikul; Haque, Tanjina Noor; Begum, Noorjahan; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Islam, Nafisa Nawal; Islam, Mohammad Sazzadul; Sultana, Nusrat; Jony, Manjur Hossain Khan; Khanam, Farhana; Mowla, Golam; Matin, Abdul; Begum, Firoza; Shirin, Tahmina; Ahmed, Dilruba; Saha, Narayan; Qadri, Firdausi

2017-01-01

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had

The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis

PubMed Central

Kash, John C.; Taubenberger, Jeffery K.

2016-01-01

Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. PMID:25747532

Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

MedlinePlus

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Targeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication

PubMed Central

Bailly, B.; Richard, C.-A.; Sharma, G.; Wang, L.; Johansen, L.; Cao, J.; Pendharkar, V.; Sharma, D.-C.; Galloux, M.; Wang, Y.; Cui, R.; Zou, G.; Guillon, P.; von Itzstein, M.; Eléouët, J.-F.; Altmeyer, R.

2016-01-01

Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti-termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection. PMID:27194388

Respiratory Infections during SARS Outbreak, Hong Kong, 2003

PubMed Central

Lo, Janice Y.C.; Tsang, Thomas H.F.; Leung, Yiu-Hong; Yeung, Eugene Y.H.; Wu, Thomson

2005-01-01

The effect of community hygienic measures during the outbreak of severe acute respiratory syndrome in Hong Kong was studied by comparing the proportion of positive specimens of various respiratory viruses in 2003 with those from 1998 to 2002. Community hygienic measures significantly reduced the incidence of various respiratory viral infections. PMID:16318726

Detection of Viral and Bacterial Pathogens in Hospitalized Children With Acute Respiratory Illnesses, Chongqing, 2009–2013

PubMed Central

Wei, Lan; Liu, Wei; Zhang, Xiao-Ai; Liu, En-Mei; Wo, Yin; Cowling, Benjamin J.; Cao, Wu-Chun

2015-01-01

Abstract Acute respiratory infections (ARIs) cause large disease burden each year. The codetection of viral and bacterial pathogens is quite common; however, the significance for clinical severity remains controversial. We aimed to identify viruses and bacteria in hospitalized children with ARI and the impact of mixed detections. Hospitalized children with ARI aged ≤16 were recruited from 2009 to 2013 at the Children's Hospital of Chongqing Medical University, Chongqing, China. Nasopharyngeal aspirates (NPAs) were collected for detection of common respiratory viruses by reverse transcription polymerase chain reaction (RT-PCR) or PCR. Bacteria were isolated from NPAs by routine culture methods. Detection and codetection frequencies and clinical features and severity were compared. Of the 3181 hospitalized children, 2375 (74.7%) were detected with ≥1 virus and 707 (22.2%) with ≥1 bacteria, 901 (28.3%) with ≥2 viruses, 57 (1.8%) with ≥2 bacteria, and 542 (17.0%) with both virus and bacteria. The most frequently detected were Streptococcus pneumoniae, respiratory syncytial virus, parainfluenza virus, and influenza virus. Clinical characteristics were similar among different pathogen infections for older group (≥6 years old), with some significant difference for the younger. Cases with any codetection were more likely to present with fever; those with ≥2 virus detections had higher prevalence of cough; cases with virus and bacteria codetection were more likely to have cough and sputum. No significant difference in the risk of pneumonia, severe pneumonia, and intensive care unit admission were found for any codetection than monodetection. There was a high codetection rate of common respiratory pathogens among hospitalized pediatric ARI cases, with fever as a significant predictor. Cases with codetection showed no significant difference in severity than those with single pathogens. PMID:25906103

School absenteeism among school-aged children with medically attended acute viral respiratory illness during three influenza seasons, 2012-2013 through 2014-2015.

PubMed

McLean, Huong Q; Peterson, Siri H; King, Jennifer P; Meece, Jennifer K; Belongia, Edward A

2017-05-01

Acute respiratory illnesses (ARIs) are common in school-aged children, but few studies have assessed school absenteeism due to specific respiratory viruses. To evaluate school absenteeism among children with medically attended ARI due to common viruses. We analyzed follow-up surveys from children seeking care for acute respiratory illness who were enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during the 2012-2013 through 2014-2015 influenza seasons. Archived influenza-negative respiratory swabs were retested using multiplex RT-PCR to detect 16 respiratory virus targets. Negative binomial and logistic regression models were used to examine the association between school absence and type of respiratory viruses; endpoints included mean days absent from school and prolonged (>2 days) absence. We examined the association between influenza vaccination and school absence among children with RT-PCR-confirmed influenza. Among 1027 children, 2295 days of school were missed due to medically attended ARIs; influenza accounted for 39% of illness episodes and 47% of days missed. Mean days absent were highest for influenza (0.96-1.19) and lowest for coronavirus (0.62). Children with B/Yamagata infection were more likely to report prolonged absence than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and 1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status was not associated with prolonged absence. School absenteeism due to medically attended ARIs varies by viral infection. Influenza B infections accounted for the greatest burden of absenteeism. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP)

PubMed Central

Park, Kyoung Un; Lee, Sang Hoon; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek

2018-01-01

Background Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Methods Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Results Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results. Conclusions The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection. PMID:29447204

Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children.

PubMed

Ahout, Inge M L; Brand, Kim H; Zomer, Aldert; van den Hurk, Wilhelma H; Schilders, Geurt; Brouwer, Marianne L; Neeleman, Chris; Groot, Ronald de; Ferwerda, Gerben

2017-06-30

Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4-6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017

Respiratory Viral Infection in Neonatal Piglets Causes Marked Microglia Activation in the Hippocampus and Deficits in Spatial Learning

PubMed Central

Elmore, Monica R. P.; Burton, Michael D.; Conrad, Matthew S.; Rytych, Jennifer L.; Van Alstine, William G.

2014-01-01

Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II+ 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II+. PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important. PMID:24501353

Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Interacts with Nsp9 and Cellular DHX9 To Regulate Viral RNA Synthesis.

PubMed

Liu, Long; Tian, Jiao; Nan, Hao; Tian, Mengmeng; Li, Yuan; Xu, Xiaodong; Huang, Baicheng; Zhou, Enmin; Hiscox, Julian A; Chen, Hongying

2016-06-01

Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N) protein is the main component of the viral capsid to encapsulate viral RNA, and it is also a multifunctional protein involved in the regulation of host cell processes. Nonstructural protein 9 (Nsp9) is the RNA-dependent RNA polymerase that plays a critical role in viral RNA transcription and replication. In this study, we demonstrate that PRRSV N protein is bound to Nsp9 by protein-protein interaction and that the contacting surface on Nsp9 is located in the two predicted α-helixes formed by 48 residues at the C-terminal end of the protein. Mutagenesis analyses identified E646, E608, and E611 on Nsp9 and Q85 on the N protein as the pivotal residues participating in the N-Nsp9 interaction. By overexpressing the N protein binding fragment of Nsp9 in infected Marc-145 cells, the synthesis of viral RNAs, as well as the production of infectious progeny viruses, was dramatically inhibited, suggesting that Nsp9-N protein association is involved in the process of viral RNA production. In addition, we show that PRRSV N interacts with cellular RNA helicase DHX9 and redistributes the protein into the cytoplasm. Knockdown of DHX9 increased the ratio of short subgenomic mRNAs (sgmRNAs); in contrast, DHX9 overexpression benefited the synthesis of longer sgmRNAs and the viral genomic RNA (gRNA). These results imply that DHX9 is recruited by the N protein in PRRSV infection to regulate viral RNA synthesis. We postulate that N and DHX9 may act as antiattenuation factors for the continuous elongation of nascent transcript during negative-strand RNA synthesis. It is unclear whether the N protein of PRRSV is involved in regulation of the viral RNA production process. In this report, we demonstrate that the N protein of the arterivirus PRRSV participates in viral RNA replication and transcription through interacting with Nsp9 and its RdRp and recruiting cellular RNA helicase to promote the production of

Seroprevalence of viral and bacterial diseases among the bovines in Himachal Pradesh, India

PubMed Central

Katoch, Shailja; Dohru, Shweta; Sharma, Mandeep; Vashist, Vikram; Chahota, Rajesh; Dhar, Prasenjit; Thakur, Aneesh; Verma, Subhash

2017-01-01

Aim: The study was designed to measure the seroprevalence of viral and bacterial diseases: Infectious bovine rhinotracheitis, bovine viral diarrhea, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, brucellosis, and paratuberculosis among bovine of Himachal Pradesh during the year 2013-2015. Materials and Methods: The serum samples were collected from seven districts of state, namely, Bilaspur, Kangra, Kinnaur, Lahul and Spiti, Mandi, Sirmour, and Solan. The samples were screened using indirect ELISA kits to measure the seroprevalence of viral and bacterial diseases. Results: The overall seroprevalence of infectious bovine rhinotracheitis was 24.24%, bovine viral diarrhea 1.52%, bovine leukemia 9.09%, bovine parainfluenza 57.58%, bovine respiratory syncytial disease 50%, brucellosis 19.69%, and paratuberculosis 9.09% in Himachal Pradesh. The seroprevalence of bovine rhinotracheitis, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, and paratuberculosis in the state varied significantly (p<0.01) while was insignificant for bovine viral diarrhea and brucellosis (p>0.01). Multiple seropositivity has been observed in this study. Bovine parainfluenza virus 3 was observed commonly in mixed infection with almost all viruses and bacteria under study. Conclusion: The viral and bacterial diseases are prevalent in the seven districts of Himachal Pradesh investigated in the study. Therefore, appropriate management practices and routine vaccination programs should be adopted to reduce the prevalence of these diseases. PMID:29391682

Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis.

PubMed

Hendricks, Matthew R; Bomberger, Jennifer M

2016-05-01

Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective.

PubMed

Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy

2016-02-15

Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

[The respiratory effects of smoking].

PubMed

Peiffer, G; Underner, M; Perriot, J

2018-06-01

A marked increase in the morbidity and mortality of a large number of broncho-pulmonary diseases has been documented in relation to smoking. The influence of tobacco smoking on various respiratory conditions. is discussed: incidence, severity or natural history modification of some respiratory illnesses: obstructive lung diseases (COPD, asthma), lung cancer, bacterial, viral respiratory infections, with the impact of smoking on tuberculosis. Finally, the relationship of tobacco with diffuse interstitial lung disease: protective role of smoking (controversial in sarcoidosis, real in hypersensitivity pneumonitis). The benefits of smoking cessation are described. Copyright © 2018. Published by Elsevier Masson SAS.

New respiratory virus (chicken pox, influenza and respiratory syncytial virus) vaccines: efficacy, necessity and policy for the tropical world at present.

PubMed

Wiwanitkit, Viroj

2009-09-01

Several respiratory viruses are documented in medicine. Several infectious diseases due to these viruses are current global public health problems. Prevention of respiratory viral infections becomes the focus of the public health ministries of many tropical countries. Presently, there are many new vaccines for respiratory viruses. These vaccines include chicken pox vaccine, influenza vaccine and respiratory syncytial virus vaccine. In this article, the author will briefly discuss on these quoted vaccines focusing on efficacy, necessity and policy for tropical world at present.

[Respiratory infections caused by respiratory syncytial virus in the adult population: description of 16 cases].

PubMed

Reina, Jordi; López, Carla

2013-08-17

Respiratory infections of viral etiology are frequent in the adult population. Those caused by respiratory syncytial virus (RSV) are a little known entity. The aim of this study was to determine the clinical and epidemiological characteristics of adult patients with respiratory infection due to RSV. We performed a prospective study from October 2012 to March 2013 on respiratory infections caused by RSV. Viral detection was performed using a technique of reverse transcription polymerase chain reaction genomic amplification in real time. We diagnosed 16 patients, 12 (75%) requiring hospitalization. Patients were grouped into immunocompromised (7 [43.7%]) and immunocompetent cases (9 cases 56.3%]). The first group included 3 patients with HIV infection (42.8%) and 4 hematologic patients (57.2%). The second group included those who had a baseline disease, 5 cases (55.5%), and those who lacked it, 4 cases (44.4%), and did not require hospitalization. The main clinical manifestations of patients prompting them to attend the Emergency Department were cough (50%), dyspnea (43.5%), fever (25%), expectoration (25%) and flu symptoms (25%). The most frequent diagnoses at discharge were pneumonia (37.5%) and flu syndrome (31.2%). Respiratory infections caused by RSV represent a rare condition that mainly affects immunocompromised patients. The underlying pathology determines the evolution of the process, which is favorable except in cases of severe immunosuppression. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Simultaneous influenza and respiratory syncytial virus infection in human respiratory tract

NASA Astrophysics Data System (ADS)

Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

2015-03-01

Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is not uncommon in hospitalized patients, although it is not clear whether these infections are more or less severe than single infections. We use mathematical models to study the dynamics of simultaneous influenza (flu) and respiratory syncytial virus (RSV) infection, two of the more common respiratory viruses, in an effort to understand simultaneous infections. We examine the roles of initial viral inoculum, relative starting time, and cell regeneration on the severity of the infection. We also study the effect of antiviral treatment on the course of the infection. This study shows that, unless treated with antivirals, flu always takes over the infection no matter how small the initial dose and how delayed it starts with respect to RSV.

A review of infectious bovine rhinotracheitis, shipping fever pneumonia and viral-bacterial synergism in respiratory disease of cattle.

PubMed Central

Yates, W D

1982-01-01

Unanswered questions on the etiology and prevention of shipping fever pneumonia have allowed this disease to remain one of the most costly to the North American cattle industry. Research in this area has indirected that while Pasteurella haemolytica and, to a lesser extent, P. multocida are involved in most cases, they seem to require additional factors to help initiate the disease process. Bovine herpes virus 1 has been shown experimentally to be one such factor. This review examines in some detail the topics of infectious bovine rhinotracheitis, shipping fever, and viral-bacterial interactions in the production of respiratory disease in various species. It deals with history, definitions, etiologies, clinical signs and lesions, and considers exposure levels, transmission and various pathogenetic mechanisms that are postulated or known to occur. PMID:6290011

Etiology of Acute Respiratory Infections in Infants: A Prospective Birth Cohort Study.

PubMed

Kumar, Prawin; Medigeshi, Guruprasad R; Mishra, Vishnu S; Islam, Mojahidul; Randev, Shivani; Mukherjee, Aparna; Chaudhry, Rama; Kapil, Arti; Ram Jat, Kana; Lodha, Rakesh; Kabra, Sushil K

2017-01-01

There is paucity of studies on etiology of acute respiratory infections (ARI) in infants. The objective of this study is to document incidence and etiology of ARI in infants, their seasonal variability and association of clinical profile with etiology. A birth cohort was followed for the first year of life; for each episode of ARI, nasopharyngeal aspirates were collected to identify the causative respiratory virus(es) using multiplex real-time polymerase chain reaction assay. For lower respiratory tract infections blood culture, serum procalcitonin, serum antibodies to Mycoplasma and Chlamydia and urinary Streptococcus pneumoniae antigen were also assayed. A total of 503 ARI episodes were documented in 310 infants for an incidence rate of 1.8 episodes per infant per year. Of these, samples were processed in 395 episodes (upper respiratory tract infection: 377; lower respiratory tract infection: 18). One or more viruses were detected in 250 (63.3%) episodes and viral coinfections in 72 (18.2%) episodes. Rhinovirus was the most common virus [105 (42%)] followed by respiratory syncytial virus [50 (20%)], parainfluenza virus [42 (16.8%)] and coronavirus [44 (17.6%)]. In lower respiratory tract infections, viral infections were detected in 12 (66.7%) episodes, bacterial infections in 17 (94.4%) episodes and mixed bacterial-viral infections in 8 (44.4%) episodes. Peak incidence of viruses was observed during February-March and September-November. There was no significant difference in symptom duration with virus types. In this cohort of infants, ARI incidence was 1.8 episodes per year per infant; 95% were upper respiratory tract infections. Viruses were identified in 63.3% episodes, and the most common viruses detected were rhinovirus, respiratory syncytial virus and parainfluenza virus.

Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children.

PubMed

Moesker, Fleur M; van Kampen, Jeroen J A; van Rossum, Annemarie M C; de Hoog, Matthijs; Koopmans, Marion P G; Osterhaus, Albert D M E; Fraaij, Pieter L A

2016-01-01

Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.

Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?

PubMed Central

Taboada, Blanca; Espinoza, Marco A.; Isa, Pavel; Aponte, Fernando E.; Arias-Ortiz, María A.; Monge-Martínez, Jesús; Rodríguez-Vázquez, Rubén; Díaz-Hernández, Fidel; Zárate-Vidal, Fernando; Wong-Chew, Rosa María; Firo-Reyes, Verónica; del Río-Almendárez, Carlos N.; Gaitán-Meza, Jesús; Villaseñor-Sierra, Alberto; Martínez-Aguilar, Gerardo; Salas-Mier, Ma. del Carmen; Noyola, Daniel E.; Pérez-Gónzalez, Luis F.; López, Susana; Santos-Preciado, José I.; Arias, Carlos F.

2014-01-01

Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low. PMID:25412469

Community-acquired respiratory infections are common in patients with non-Hodgkin lymphoma and multiple myeloma.

PubMed

Lavi, Noa; Avivi, Irit; Kra-Oz, Zipora; Oren, Ilana; Hardak, Emilia

2018-07-01

Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis. Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed. One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age < 60 years, MM diagnosis, and autologous SCT increased the respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated. Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

Does atopy affect the course of viral pneumonia?

PubMed

Erdem, S B; Can, D; Girit, S; Çatal, F; Şen, V; Pekcan, S; Yüksel, H; Bingöl, A; Bostancı, I; Erge, D; Ersu, R

The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild-moderate and severe according to the course of pneumonia. Presence of atopy was evaluated with skin prick tests. Groups were compared to evaluate the risk factors associated with severe viral pneumonia. A total of 280 patients from nine centres were included in the study. Of these patients, 163 (58.2%) were male. Respiratory syncytial virus (29.7%), Influenza A (20.5%), rhinovirus (18.9%), adenovirus (10%), human metapneumovirus (8%), parainfluenza (5.2%), coronavirus (6%), and bocavirus (1.6%) were isolated from respiratory samples. Eighty-five (30.4%) children had severe pneumonia. Atopic sensitisation was found in 21.4% of the patients. Ever wheezing (RR: 1.6, 95% CI: 1.1-2.4), parental asthma (RR: 1.5, 95% CI: 1.1-2.2), other allergic diseases in the family (RR: 1.8, 95% CI: 1.2-2.9) and environmental tobacco smoke (RR: 1.6, 95% CI: 1.1-3.5) were more common in the severe pneumonia group. When patients with mild-moderate pneumonia were compared to patients with severe pneumonia, frequency of atopy was not different between the two groups. However, parental asthma, ever wheezing and environmental tobacco smoke exposure are risk factors for severe viral pneumonia in children. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Helper T Cell Responses to Respiratory Viruses in the Lung: Development, Virus Suppression, and Pathogenesis.

PubMed

Miyauchi, Kosuke

The lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. Lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. Once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. Innate immune signaling also activates virus-specific adaptive immune responses. The helper T cells play pivotal roles in the humoral and cellular adaptive immune responses. Helper T cells are categorized into several distinct subsets (e.g., T H 1, T H 2, T FH , T H 17, and Treg), differentiated by their corresponding signature cytokine production profiles. Helper T cells migrate into the airways and the lung after respiratory virus infections. The behavior of the helper T cells differs with each respiratory virus-in some cases, the response is beneficial; in other cases, it is harmful. Here, the general mechanisms underlying helper T cell responses to viral infections are summarized, and functions and reactions of the helper T cells against some respiratory viral infections are discussed. In influenza virus infections, T H 1 cells, which regulate the cytotoxic T lymphocytes and IgG2 responses, are efficiently activated. T FH cells required for highly specific and memory humoral responses are also activated on influenza infections. In infections with respiratory syncytial virus and rhinovirus, T H 2 cells develop in the lung and contribute to pathogenesis. In many cases, Treg cells inhibit excessive virus-specific T cell responses that can contribute to viral pathogenicity.

β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

PubMed

Wu, Pingsheng; Larkin, Emma K; Reiss, Sara S; Carroll, Kecia N; Summar, Marshall L; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Islam, Jessica Y; Hartert, Tina V; Moore, Paul E

2015-09-14

Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence

Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

PubMed

Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

2017-09-15

Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season.

PubMed

Zimmerman, Richard K; Rinaldo, Charles R; Nowalk, Mary Patricia; Gk, Balasubramani; Thompson, Mark G; Moehling, Krissy K; Bullotta, Arlene; Wisniewski, Stephen

2014-07-01

Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. During January-April 2012, outpatients with acute respiratory illness (≤ 7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. Among 662 participants (6 months-82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥ 50 years (P = 0.01), fever was more common in hMPV and influenza infections (P = 0.008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher among those with influenza (P = 0.036). Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Respiratory Support in Bronchiolitis: Trial Evidence.

PubMed

Cunningham, Steve

2018-05-01

Acute viral lower respiratory tract infection is frequently associated with hypoxemia and respiratory distress, sometimes progressing to hypercarbia and respiratory failure. In recent years, trials have assessed the effects of oxygen supplementation and respiratory support with high-flow oxygen therapy. An oxygen saturation target of 90% is as safe and clinically effective as 94% in infants with bronchiolitis. Trials of high-flow humidified oxygen have demonstrated safety, but as yet poorly demarcated an appropriate place for use within the clinical course of the disease. Effective trials of continuous positive airway pressure are lacking and urgently required. The trials reported to date have highlighted the need for common outcomes in relation to treatment failure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review.

PubMed

Zheng, Xue-Yan; Xu, Yan-Jun; Guan, Wei-Jie; Lin, Li-Feng

2018-04-01

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.

Host response to bovine respiratory pathogens.

PubMed

Czuprynski, Charles J

2009-12-01

Bovine respiratory disease (BRD) involves complex interactions amongst viral and bacterial pathogens that can lead to intense pulmonary inflammation (fibrinous pleuropneumonia). Viral infection greatly increases the susceptibility of cattle to secondary infection of the lung with bacterial pathogens like Mannheimia haemolytica and Histophilus somni. The underlying reason for this viral/bacterial synergism, and the manner in which cattle respond to the virulence strategies of the bacterial pathogens, is incompletely understood. Bovine herpesvirus type 1 (BHV-1) infection of bronchial epithelial cells in vitro enhances the binding of M. haemolytica and triggers release of inflammatory mediators that attract and enhance binding of neutrophils. An exotoxin (leukotoxin) released from M. haemolytica further stimulates release of inflammatory mediators and causes leukocyte death. Cattle infected with H. somni frequently display vasculitis. Exposure of bovine endothelial cells to H. somnii or its lipooligosaccharide (LOS) increases endothelium permeability, and makes the surface of the endothelial cells pro-coagulant. These processes are amplified in the presence of platelets. The above findings demonstrate that bovine respiratory pathogens (BHV-1, M. haemolytica and H. somni) interact with leukocytes and other cells (epithelial and endothelial cells) leading to the inflammation that characterizes BRD.

Bayesian evidence and epidemiological implications of environmental contamination from acute respiratory infection in long-term care facilities.

PubMed

Diaz-Decaro, J D; Launer, B; Mckinnell, J A; Singh, R; Dutciuc, T D; Green, N M; Bolaris, M; Huang, S S; Miller, L G

2018-05-01

Skilled nursing home facilities (SNFs) house a vulnerable population frequently exposed to respiratory pathogens. Our study aims to gain a better understanding of the transmission of nursing home-acquired viral respiratory infections in non-epidemic settings. Symptomatic surveillance was performed in three SNFs for residents exhibiting acute respiratory symptoms. Environmental surveillance of five high-touch areas was performed to assess possible transmission. All resident and environmental samples were screened using a commercial multiplex polymerase chain reaction platform. Bayesian methods were used to evaluate environmental contamination. Among nursing home residents with respiratory symptoms, 19% had a detectable viral pathogen (parainfluenza-3, rhinovirus/enterovirus, RSV, or influenza B). Environmental contamination was found in 20% of total room surface swabs of symptomatic residents. Environmental and resident results were all concordant. Target period prevalence among symptomatic residents ranged from 5.5 to 13.3% depending on target. Bayesian analysis quantifies the probability of environmental shedding due to parainfluenza-3 as 92.4% (95% CI: 86.8-95.8%) and due to rhinovirus/enterovirus as 65.6% (95% CI: 57.9-72.5%). Our findings confirm that non-epidemic viral infections are common among SNF residents exhibiting acute respiratory symptoms and that environmental contamination may facilitate further spread with considerable epidemiological implications. Findings further emphasise the importance of environmental infection control for viral respiratory pathogens in long-term care facilities.

[Prevention of the recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections].

PubMed

Kuznetzova, O Yu; Gorshenina, A P; Maximovskaya, L N

Research objective was to study the efficacy of ingavirin for prevention of recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections. 128 employees aged from 18 to 56 years were included in the study. Clinical and immunological efficiency of ingavirin prevention of recurrent herpetic stomatitis is proved by estimation of oral cavity local immunity (SlgA, lisozyme), humoral immunity (IgE and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). After administration of ingavirin significant (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes and IgG concentration was observed. The obtained data allow to recommend ingavirin for prevention of recurrent herpetic stomatitis.

The rapid diagnosis of viral respiratory tract infections and its impact on antimicrobial stewardship programs.

PubMed

Keske, Şiran; Ergönül, Önder; Tutucu, Faik; Karaaslan, Doruk; Palaoğlu, Erhan; Can, Füsun

2018-04-01

We aimed to describe the potential benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use among the inpatients presenting with influenza-like illness (ILI). We included patients from inpatient and outpatient departments who had ILI and performed MRT between 1 January 2015 and 31 December 2016 in a 265-bed private hospital in Istanbul. At the end of 2015, we implemented antimicrobial stewardship including systematic use of MRT. Then, we compared our observations between the year 2015 and the year 2016. We designed the study according to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) tool. A U.S. Food and Drug Administration (FDA)-cleared multiplexed polymerase chain reaction (PCR) system (BioFire FilmArray, Idaho Technology, Salt Lake City, UT) which detects 17 viruses and three bacteria was used for diagnosis. In total, 1317 patients were included; 630 (48%) were inpatients and 569 (43%) were older than 16 years of age. At least one virus was detected in 747 (57%) patients. Rhinovirus/enterovirus, influenza virus, and adenovirus were the most commonly detected. Among hospitalized patients, in children, a significant decrease in antibiotic use (44.5% in 2015 and 28.8% in 2016, p = 0.009) was observed, but in adults, the decrease was not statistically significant (72% in 2015 and 63% in 2016, p = 0.36). The duration of antibiotic use after the detection of virus was significantly decreased in both children and adults (p < 0.001 and p = 0.007, respectively). By using MRT, inappropriate antibiotic use and, also, duration of inappropriate antibiotic use after the detection of virus was significantly decreased. It is time to increase the awareness about the viral etiology in respiratory tract infections (RTIs) and implement MRT in clinical practice.

Integrated DNA and RNA extraction and purification on an automated microfluidic cassette from bacterial and viral pathogens causing community-acquired lower respiratory tract infections.

PubMed

Van Heirstraeten, Liesbet; Spang, Peter; Schwind, Carmen; Drese, Klaus S; Ritzi-Lehnert, Marion; Nieto, Benjamin; Camps, Marta; Landgraf, Bryan; Guasch, Francesc; Corbera, Antoni Homs; Samitier, Josep; Goossens, Herman; Malhotra-Kumar, Surbhi; Roeser, Tina

2014-05-07

In this paper, we describe the development of an automated sample preparation procedure for etiological agents of community-acquired lower respiratory tract infections (CA-LRTI). The consecutive assay steps, including sample re-suspension, pre-treatment, lysis, nucleic acid purification, and concentration, were integrated into a microfluidic lab-on-a-chip (LOC) cassette that is operated hands-free by a demonstrator setup, providing fluidic and valve actuation. The performance of the assay was evaluated on viral and Gram-positive and Gram-negative bacterial broth cultures previously sampled using a nasopharyngeal swab. Sample preparation on the microfluidic cassette resulted in higher or similar concentrations of pure bacterial DNA or viral RNA compared to manual benchtop experiments. The miniaturization and integration of the complete sample preparation procedure, to extract purified nucleic acids from real samples of CA-LRTI pathogens to, and above, lab quality and efficiency, represent important steps towards its application in a point-of-care test (POCT) for rapid diagnosis of CA-LRTI.

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity.

PubMed

Perez, Geovanny F; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E; Rose, Mary C; Pillai, Dinesh; Nino, Gustavo

2016-10-20

Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32-37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

PubMed Central

Perez, Geovanny F.; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E.; Rose, Mary C.; Pillai, Dinesh; Nino, Gustavo

2016-01-01

Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life. PMID:27775602

Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016.

PubMed

Lau, Yuk-Fai; Koh, Wee-Hong Victor; Kan, Clement; Dua, Poh-Choo Alethea; Lim, Ai-Sim Elizabeth; Liaw, Chin-Wen Jasper; Gao, Qiu-Han; Chng, Jeremiah; Lee, Vernon J; Tan, Boon-Huan; Loh, Jin-Phang

2018-03-12

Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a

Circulating microRNAs in serum from cattle challenged with Bovine Viral Diarrhea Virus

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) is an RNA virus that is often associated with respiratory disease in cattle. MicroRNAs have been proposed as indicators of exposure to respiratory pathogens. The objective of this study was to identify microRNAs in cattle that had been challenged with a non-cytopat...

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

PubMed

Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

2017-10-01

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T H 2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T H 2 mediators. With the renewed interest in anti-T H 2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells

PubMed Central

Lin, C.; Agnes, J. T.; Behrens, N.; Tagawa, Y.; Gershwin, L. J.; Corbeil, L. B.

2016-01-01

Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2—RSAD2) and ISG15 (IFN-stimulated gene 15—ubiquitin-like modifier) were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo. PMID:26859677

Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

PubMed

Lin, C; Agnes, J T; Behrens, N; Shao, M; Tagawa, Y; Gershwin, L J; Corbeil, L B

2016-01-01

Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2) and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier) were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

Detection of common diarrhea-causing pathogens in Northern Taiwan by multiplex polymerase chain reaction.

PubMed

Huang, Shu-Huan; Lin, Yi-Fang; Tsai, Ming-Han; Yang, Shuan; Liao, Mei-Ling; Chao, Shao-Wen; Hwang, Cheng-Cheng

2018-06-01

Conventional methods for identifying gastroenteritis pathogens are time consuming, more likely to result in a false-negative, rely on personnel with diagnostic expertise, and are dependent on the specimen status. Alternatively, molecular diagnostic methods permit the rapid, simultaneous detection of multiple pathogens with high sensitivity and specificity. The present study compared conventional methods with the Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for the diagnosis of infectious gastroenteritis in northern Taiwan. From July 2015 to April 2016, 217 clinical fecal samples were collected from patients with suspected infectious gastroenteritis. All specimens were tested using conventional diagnostic techniques following physicians' orders as well as with the xTAG GPP. The multiplex polymerase chain reaction (PCR) approach detected significantly more positive samples with bacterial, viral, and/or parasitic infections as compared to conventional analysis (55.8% vs 40.1%, respectively; P < .001). Moreover, multiplex PCR could detect Escherichia coli O157, enterotoxigenic E coli, Shiga-like toxin-producing E coli, Cryptosporidium, and Giardia, which were undetectable by conventional methods. Furthermore, 48 pathogens in 23 patients (10.6%) with coinfections were identified only using the multiplex PCR approach. Of which, 82.6% were from pediatric patients. Because the detection rates using multiplex PCR are higher than conventional methods, and some pediatric pathogens could only be detected by multiplex PCR, this approach may be useful in rapidly diagnosing diarrheal disease in children and facilitating treatment initiation. Further studies are necessary to determine if multiplex PCR improves patient outcomes and reduces costs.

Detection of common diarrhea-causing pathogens in Northern Taiwan by multiplex polymerase chain reaction

PubMed Central

Huang, Shu-Huan; Lin, Yi-Fang; Tsai, Ming-Han; Yang, Shuan; Liao, Mei-Ling; Chao, Shao-Wen; Hwang, Cheng-Cheng

2018-01-01

Abstract Conventional methods for identifying gastroenteritis pathogens are time consuming, more likely to result in a false-negative, rely on personnel with diagnostic expertise, and are dependent on the specimen status. Alternatively, molecular diagnostic methods permit the rapid, simultaneous detection of multiple pathogens with high sensitivity and specificity. The present study compared conventional methods with the Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for the diagnosis of infectious gastroenteritis in northern Taiwan. From July 2015 to April 2016, 217 clinical fecal samples were collected from patients with suspected infectious gastroenteritis. All specimens were tested using conventional diagnostic techniques following physicians’ orders as well as with the xTAG GPP. The multiplex polymerase chain reaction (PCR) approach detected significantly more positive samples with bacterial, viral, and/or parasitic infections as compared to conventional analysis (55.8% vs 40.1%, respectively; P < .001). Moreover, multiplex PCR could detect Escherichia coli O157, enterotoxigenic E coli, Shiga-like toxin-producing E coli, Cryptosporidium, and Giardia, which were undetectable by conventional methods. Furthermore, 48 pathogens in 23 patients (10.6%) with coinfections were identified only using the multiplex PCR approach. Of which, 82.6% were from pediatric patients. Because the detection rates using multiplex PCR are higher than conventional methods, and some pediatric pathogens could only be detected by multiplex PCR, this approach may be useful in rapidly diagnosing diarrheal disease in children and facilitating treatment initiation. Further studies are necessary to determine if multiplex PCR improves patient outcomes and reduces costs. PMID:29879060

MicroRNA expression profiling in tonsils of calves challenged with a laboratory strain or field isolates of Bovine Respiratory Syncytial Virus

USDA-ARS?s Scientific Manuscript database

Bovine respiratory syncytial virus (BRSV) is a leading cause of bovine respiratory disease in cattle worldwide. MicroRNAs have been suggested to play a role in viral infections via their regulation of cellular molecules involved in either viral replication or in host innate immunity to infection. Th...

Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response▿

PubMed Central

Glowacka, Ilona; Bertram, Stephanie; Müller, Marcel A.; Allen, Paul; Soilleux, Elizabeth; Pfefferle, Susanne; Steffen, Imke; Tsegaye, Theodros Solomon; He, Yuxian; Gnirss, Kerstin; Niemeyer, Daniela; Schneider, Heike; Drosten, Christian; Pöhlmann, Stefan

2011-01-01

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Finally, ACE2, the cellular receptor for SARS-CoV, and TMPRSS2 were found to be coexpressed by type II pneumocytes, which represent important viral target cells, suggesting that SARS S is cleaved by TMPRSS2 in the lung of SARS-CoV-infected individuals. In summary, we show that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion. PMID:21325420

Incidence and etiology of hospitalized acute respiratory infections in the Egyptian Delta.

PubMed

Rowlinson, Emily; Dueger, Erica; Mansour, Adel; Azzazy, Nahed; Mansour, Hoda; Peters, Lisa; Rosenstock, Summer; Hamid, Sarah; Said, Mayar M; Geneidy, Mohamed; Abd Allah, Monier; Kandeel, Amr

2017-01-01

Acute Respiratory Infections (ARI) are responsible for nearly two million childhood deaths worldwide. A limited number of studies have been published on the epidemiology of viral respiratory pathogens in Egypt. A total of 6113 hospitalized patients >1 month of age with suspected ARI were enrolled between June 23, 2009 and December 31, 2013. Naso- and oropharyngeal specimens were collected and tested for influenza A and B, respiratory syncytial virus, human metapneumovirus, adenovirus, and parainfluenza viruses 1-3. Blood specimens from children 1-11 months were cultured and bacterial growth was identified by polymerase chain reaction. Results from a healthcare utilization survey on the proportion of persons seeking care for ARI was used to calculate adjusted ARI incidence rates in the surveillance population. The proportion of patients with a viral pathogen detected decreased with age from 67% in patients age 1-11 months to 19% in patients ≥65 years of age. Influenza was the dominant viral pathogen detected in patients ≥1 year of age (13.9%). The highest incidence rates for hospitalized ARI were observed in children 1-11 months (1757.9-5537.5/100 000 population) and RSV was the most commonly detected pathogen in this age group. In this study population, influenza is the largest viral contributor to hospitalized ARIs and children 1-11 months of age experience a high rate of ARI hospitalizations. This study highlights a need for surveillance of additional viral pathogens and alternative detection methods for bacterial pathogens, which may reveal a substantial proportion of as yet unidentified etiologies in adults. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Phosphorylation of paramyxovirus phosphoprotein and its role in viral gene expression.

PubMed

Fuentes, Sandra M; Sun, Dengyun; Schmitt, Anthony P; He, Biao

2010-01-01

Paramyxoviruses include many important human and animal pathogens such as measles virus, mumps virus, human parainfluenza viruses, and respiratory syncytial virus, as well as emerging viruses such as Nipah virus and Hendra virus. The paramyxovirus RNA-dependent RNA polymerase consists of the phosphoprotein (P) and the large protein. Both of these proteins are essential for viral RNA synthesis. The P protein is phosphorylated at multiple sites, probably by more than one host kinase. While it is thought that the phosphorylation of P is important for its role in viral RNA synthesis, the precise role of P protein phosphorylation remains an enigma. For instance, it was demonstrated that the putative CKII phosphorylation sites of the P protein of respiratory syncytial virus play a role in viral RNA synthesis using a minigenome replicon system; however, mutating these putative CKII phosphorylation sites within a viral genome had no effect on viral RNA synthesis, leading to the hypothesis that P protein phosphorylation, at least by CKII, does not play a role in viral RNA synthesis. Recently, it has been reported that the phosphorylation state of the P protein of parainfluenza virus 5, a prototypical paramyxovirus, correlates with the ability of P protein to synthesize viral RNA, indicating that P protein phosphorylation does in fact play a role in viral RNA synthesis. Furthermore, host kinases PLK1, as well as AKT1 have been found to play critical roles in paramyxovirus RNA synthesis through regulation of P protein phosphorylation status. Beyond furthering our understanding of paramyxovirus RNA replication, these recent discoveries may also result in a new paradigm in treating infections caused by these viruses, as host kinases that regulate paramyxovirus replication are investigated as potential targets of therapeutic intervention.

Viral etiologies of influenza-like illness and severe acute respiratory infections in Thailand.

PubMed

Chittaganpitch, Malinee; Waicharoen, Sunthareeya; Yingyong, Thitipong; Praphasiri, Prabda; Sangkitporn, Somchai; Olsen, Sonja J; Lindblade, Kim A

2018-07-01

Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. Patients with influenza-like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset <10 days, requiring hospitalization) were enrolled from 10 sites. Throat swabs were tested for influenza viruses, respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1-3, and adenoviruses by polymerase chain reaction (PCR) or real-time reverse transcriptase-PCR. We screened 15 369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases <15 years old) and 1754 cases of SARI (1404 cases <15 years old). Among ILI cases <15 years old, influenza viruses (1173, 23%), RSV (447, 9%), and adenoviruses (430, 8%) were the most frequently identified respiratory viruses tested, while for SARI cases <15 years old, RSV (196, 14%) influenza (157, 11%) and adenoviruses (90, 6%) were the most common. The RSV season significantly overlapped the larger influenza season from July to November in Thailand. The global expansion of influenza sentinel surveillance provides an opportunity to gather information on the characteristics of cases positive for non-influenza respiratory viruses, particularly seasonality, although adjustments to case definitions may be required. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

H1N1 Influenza Viral Infection in a Postpartum Young Woman Causes Respiratory Failure: What the Care Providers Ought to Know?

PubMed Central

Aloizos, Stavros; Aravosita, Paraskevi; Mystakelli, Christina; Kanna, Efthymia; Gourgiotis, Stavros

2012-01-01

Pregnant and postpartum women are considered a population at increased risk of hospitalization of H1N1 infection. We report the case of a young postpartum woman, who developed evidence of respiratory failure reaching the point of requiring intubation due to an H1N1 influenza virus infection two days after a caesarean delivery. We emphasize the diagnosis, management, and the outcome focusing on the question “what the care providers, including obstetric health care workers, ought to know?” Diagnostic and management strategy for pregnant or postpartum women with novel influenza A (H1N1) viral infection and increased awareness amongst patients and health care professionals may result in improved survival. PMID:23150842

Prevalence of respiratory viruses in Iranian patients with idiopathic pulmonary fibrosis.

PubMed

Keyvani, Hossein; Moghoofei, Mohsen; Bokharaei-Salim, Farah; Mostafaei, Shayan; Javad Mousavi, Seyed-Ali; Monavari, Seyed Hamidreza; Esghaei, Maryam

2017-11-01

Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal lung disease. One of the risk factors involved in the acquisition of IPF is viral infections, especially respiratory viruses. In the present study, we investigated the detection of respiratory viruses and the possible relationship between these viruses and IPF. This cross-sectional study was supported by the Iran University of Medical Sciences (IUMS), Tehran, Iran. A total of 40 respiratory samples (five nasopharyngeal and 35 bronchoalveolar lavage specimens) were obtained from IPF patients referred to IUMS hospitals between April 2015 and December 2016. Assays were performed using the CLART Pneumovir DNA array assay, which made it possible to detect five genera of respiratory viruses simultaneously.Results/Key findings. Altogether, 22 of the 40 participants were male. Respiratory syncytial virus (RSV), parainfluenza, rhino, corona and influenza viruses were found in 2.5 % (1/40), 7.5 % (3/40), 10 % (4/40), 2.5 % (1/40) and 0% (0/40) of cases, respectively. Determining a correlation between the viruses and IPF is not an easy task, and therefore, this will require more research. In addition, the CLART Pneumovir DNA array can be considered as a useful method for simultaneous detection of several viral respiratory infections.

Novel Interventions for Bovine Respiratory Disease.

USDA-ARS?s Scientific Manuscript database

Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune and metabolic responses to a combined viral-bacterial respiratory disease challenge. Beef heifers (n = 32; 324 ± 19.2 kg BW) were selected and randomly assigned to one of two treatmen...

DIFFERENTIAL GENE EXPRESSION INDUCED BY RESPIRATORY SYNCTIAL VIRUS IN HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

Respiratory syncytial virus (RSV), a negative-stranded RNA virus, is a common viral pathogen for respiratory infection in both children and immunocompromised adults. Early host defense may play a critical role in determining the severity of the infection. To gain further insight ...

Immune evasion by pathogens of bovine respiratory disease complex.

PubMed

Srikumaran, Subramaniam; Kelling, Clayton L; Ambagala, Aruna

2007-12-01

Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

PubMed

Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

2016-06-01

Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Acupuncture therapy for fever induced by viral upper respiratory tract infection (URTI) in military medical service: a case series.

PubMed

Kwon, SeungWon; Shin, KyoungHo; Jung, WooSang; Moon, SangKwan; Cho, KiHo

2014-12-01

We report the cases of eight military patients with fever (≥38°C) induced by viral upper respiratory tract infection (URTI) who requested treatment with acupuncture in the military medical service room. All patients were treated immediately after diagnosis with classical acupuncture (GV14, GB20, TE8 points) and a new type of acupuncture, equilibrium acupuncture (Feibing and Ganmao points). After one treatment session (20 min), reduction of body temperature was confirmed in all patients. Accompanying symptoms such as headache, myalgia and nasal obstruction also showed a tendency to decrease. Within 3 days of treatment, six of the eight patients had recovered from the URTI. No adverse effects of acupuncture treatment were reported. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparison of NxTAG Respiratory Pathogen Panel and Anyplex II RV16 Tests for Multiplex Detection of Respiratory Pathogens in Hospitalized Children

PubMed Central

Brotons, Pedro; Henares, Desiree; Latorre, Irene; Cepillo, Antonio; Launes, Cristian

2016-01-01

Multiplex molecular techniques can detect a diversity of respiratory viruses and bacteria that cause childhood acute respiratory infection rapidly and conveniently. However, currently available techniques show high variation in performance. We sought to compare the diagnostic accuracy of the novel multiplex NxTAG respiratory pathogen panel (RPP) RUO test versus a routine multiplex Anyplex II RV16 assay in respiratory specimens collected from children <18 years of age hospitalized with nonspecific symptoms of acute lower respiratory infection. Parallel testing was performed on nasopharyngeal aspirates prospectively collected at referral Children's Hospital Sant Joan de Déu (Barcelona, Spain) between June and November 2015. Agreement values between the two tests and kappa coefficients were assessed. Bidirectional sequencing was performed for the resolution of discordant results. A total of 319 samples were analyzed by both techniques. A total of 268 (84.0%) of them yielded concordant results. Positive percent agreement values ranged from 83.3 to 100%, while the negative percent agreement was more than 99% for all targets except for enterovirus/rhinovirus (EV/RV; 94.4%). Kappa coefficients ranged from 0.83 to 1.00. Discrepancy analysis confirmed 66.0% of NxTAG RPP RUO results. A total of 260 viruses were detected, with EV/RV (n = 105, 40.4%) being the most prevalent target. Viral coinfections were found in 44 (14.2%) samples. In addition, NxTAG RPP RUO detected single bacterial and mixed viral-bacterial infections in seven samples. NxTAG RPP RUO showed high positive and negative agreement with Anyplex II RV16 for main viruses that cause acute respiratory infections in children, coupled with an additional capability to detect some respiratory bacteria. PMID:27629904

The impact of bacterial and viral co‐infection in severe influenza

PubMed Central

Blyth, Christopher C.; Webb, Steve A. R.; Kok, Jen; Dwyer, Dominic E.; van Hal, Sebastiaan J.; Foo, Hong; Ginn, Andrew N.; Kesson, Alison M.; Seppelt, Ian; Iredell, Jonathan R.

2013-01-01

Please cite this paper as: Blyth et al. (2013) The impact of bacterial and viral co‐infection in severe influenza. Influenza and Other Respiratory Viruses 7(2) 168–176. Background  Many questions remain concerning the burden, risk factors and impact of bacterial and viral co‐infection in patients with pandemic influenza admitted to the intensive care unit (ICU). Objectives  To examine the burden, risk factors and impact of bacterial and viral co‐infection in Australian patients with severe influenza. Patients/Methods  A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. Results  Co‐infection was identified in 23·3–26·9% of patients with severe influenza A infection: viral co‐infection, 3·2–3·4% and bacterial co‐infection, 20·5–24·7%. Staphylococcus aureus was the most frequent bacterial co‐infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co‐infection were younger [mean difference in age = 8·46 years (95% CI: 0·18–16·74 years)], less likely to have significant co‐morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77–11·96)] compared to those without co‐infection. Conclusions  Bacterial or viral co‐infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co‐infected patients being younger and with fewer co‐morbidities, no significant difference in outcomes was observed. It is likely that co‐infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease

A patented strain of Bacillus coagulans increased immune response to viral challenge.

PubMed

Baron, Mira

2009-03-01

Viral respiratory tract infection is the most common illness among humans. Probiotics have been known to enhance the immune system and, therefore, may represent a significant therapeutic advancement for treating viral respiratory tract infections. A controlled study was conducted to evaluate the effects of the patented GanedenBC30 probiotic (Bacillus coagulans GBI-30, 6086, marketed as Sustenex [Ganeden Biotech, Inc., Mayfield Heights, OH]) on the immune system when exposed to adenovirus and influenza in otherwise healthy adults. Ten healthy men and women (average age, 44 years) were instructed to consume 1 capsule of GanedenBC30 with water once a day for 30 days. At baseline and after completion of the 30-day treatment, blood levels of cytokines were measured in vitro after T-cell exposure to adenovirus and influenza A. Each participant served as his/her own control with baseline blood draw. The use of GanedenBC30 significantly increased T-cell production of TNF-alpha in response to adenovirus exposure (P = 0.027) and influenza A (H3N2 Texas strain) exposure (P = 0.004), but it did not have a significant effect on the response to other strains of influenza. No serious adverse events were reported throughout the study. The patented GanedenBC30 probiotic may be a safe and effective therapeutic option for enhancing T-cell response to certain viral respiratory tract infections.

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

PubMed

Seemungal, T; Harper-Owen, R; Bhowmik, A; Moric, I; Sanderson, G; Message, S; Maccallum, P; Meade, T W; Jeffries, D J; Johnston, S L; Wedzicha, J A

2001-11-01

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

PubMed

Głobińska, Anna; Kowalski, Marek L

2017-10-01

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Comparative transcriptome response in swine tracheobronchial lymph nodes to viral infection

USDA-ARS?s Scientific Manuscript database

The tracheobronchial lymph node (TBLN) transcriptome response was evaluated following viral infection using Digital Gene Expression Tag Profiling (DGETP). Pigs were sham-treated or infected intranasally with porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, pseudorabies...

Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

PubMed

Korten, Insa; Kieninger, Elisabeth; Klenja, Shkipe; Mack, Ines; Schläpfer, Njima; Barbani, Maria Teresa; Regamey, Nicolas; Kuehni, Claudia E; Hilty, Markus; Frey, Urs; Gorgievski, Meri; Casaulta, Carmen; Latzin, Philipp

2018-01-01

Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pitfalls in interpretation of CT-values of RT-PCR in children with acute respiratory tract infections.

PubMed

Wishaupt, Jérôme O; Ploeg, Tjeerd van der; Smeets, Leo C; Groot, Ronald de; Versteegh, Florens G A; Hartwig, Nico G

2017-05-01

The relation between viral load and disease severity in childhood acute respiratory tract infections (ARI) is not fully understood. To assess the clinical relevance of the relation between viral load, determined by cycle threshold (CT) value of real-time reverse transcription-polymerase chain reaction assays and disease severity in children with single- and multiple viral ARI. 582 children with ARI were prospectively followed and tested for 15 viruses. Correlations were calculated between CT values and clinical parameters. In single viral ARI, statistically significant correlations were found between viral loads of Respiratory Syncytial Virus (RSV) and hospitalization and between viral loads of Human Coronavirus (HCoV) and a disease severity score. In multiple-viral ARI, statistically significant correlations between viral load and clinical parameters were found. In RSV-Rhinovirus (RV) multiple infections, a low viral load of RV was correlated with a high length of hospital stay and a high duration of extra oxygen use. The mean CT value for RV, HCoV and Parainfluenza virus was significantly lower in single- versus multiple infections. Although correlations between CT values and clinical parameters in patients with single and multiple viral infection were found, the clinical importance of these findings is limited because individual differences in host-, viral and laboratory factors complicate the interpretation of statistically significant findings. In multiple infections, viral load cannot be used to differentiate between disease causing virus and innocent bystanders. Copyright © 2017 Elsevier B.V. All rights reserved.

Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway

PubMed Central

2014-01-01

Background Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. Results BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. Conclusion The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV. PMID:24423030

Identification of viral genes associated with the interferon-inducing phenotype of a synthetic porcine reproductive and respiratory syndrome virus strain.

PubMed

Sun, Haiyan; Pattnaik, Asit K; Osorio, Fernando A; Vu, Hiep L X

2016-12-01

We recently generated a fully synthetic porcine reproductive and respiratory syndrome virus strain (designated as PRRSV-CON), which confers unprecedented levels of heterologous protection. We report herein that the synthetic PRRSV-CON possesses a unique phenotype in that it induces type-I interferons (IFNs) instead of suppressing these cytokines as most of the naturally occurring PRRSV isolates do. Through gain- and loss- of-function studies, the IFN-inducing phenotype of PRRSV-CON was mapped to the 3.3kb genomic fragment encoding three viral nonstructural proteins: nsp1α, nsp1β and the N-terminal part of nsp2. Further studies indicated that a cooperation among these 3 proteins was required for effective induction of IFNs. Collectively, this study constitutes the first step toward understanding the mechanisms by which the synthetic PRRSV-CON confers heterologous protection. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

PubMed Central

2013-01-01

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

Clinical signs of dysphagia in infants with acute viral bronchiolitis☆

PubMed Central

Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

2014-01-01

Objective: To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. Methods: This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Results: Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Conclusions: Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. PMID:25479843

Aptamers in Diagnostics and Treatment of Viral Infections

PubMed Central

Wandtke, Tomasz; Woźniak, Joanna; Kopiński, Piotr

2015-01-01

Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases. PMID:25690797

Detection of viral infections using colloidal quantum dots

NASA Astrophysics Data System (ADS)

Bentzen, Elizabeth L.; House, Frances S.; Utley, Thomas J.; Crowe, James E., Jr.; Wright, David W.

2006-02-01

Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Quantum dots were used to detect and monitor the progession of viral glycoproteins, F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. Additionally, oligo-Qdot RNA probes have been developed for identification and detection of mRNA of the N(nucleocapsid) protein for RSV. The use of quantum dot-FISH probes provides another confirmatory route to diagnostics as well as a new class of probes for monitoring the flux and fate of viral RNA RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

Seasonal variations of respiratory viruses detected from children with respiratory tract infections in Riyadh, Saudi Arabia.

PubMed

Albogami, Saad S; Alotaibi, Meshal R; Alsahli, Saud A; Masuadi, Emad; Alshaalan, Mohammad

ARTIs have a huge impact in health systems in which 20-30% of all hospital admissions and 30-60% of practitioner visits are related to respiratory tract infections. The aim of this study is to determine the prevalence, age distribution, and seasonal variation of respiratory viruses. This study was descriptive retrospective study in which all patients 14 years of age and below who presented with signs and symptoms of ARTIs between January 2013 and December 2014 and had respiratory specimen tested by direct immunofluorescence assays for viruses identification were included in the study. During that period, a total of 4611 patients who presented with ARTIs from January 2013 to December 2014 were investigated, viruses were detected in 1115 (24%). RSV was associated with 97.4% of the total viral pathogens. Viruses were detected throughout all the two years with a peak in winter; Dec (n: 265), Jan (n: 418), Feb (n: 218), and Mar (n: 109). Viral pathogens are very important cause of ARTIs in our region. RSV was the most common virus detected with the highest detection rate in children who are two years old and below. A multi-center surveillance with more sensitive detection methods like PCR may help to provide a comprehensive understanding of virus distribution in our area, which may contribute implant an effective prevention approach for each virus. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute respiratory infections among returning Hajj pilgrims-Jordan, 2014.

PubMed

Al-Abdallat, Mohammad Mousa; Rha, Brian; Alqasrawi, Sultan; Payne, Daniel C; Iblan, Ibrahim; Binder, Alison M; Haddadin, Aktham; Nsour, Mohannad Al; Alsanouri, Tarek; Mofleh, Jawad; Whitaker, Brett; Lindstrom, Stephen L; Tong, Suxiang; Ali, Sami Sheikh; Dahl, Rebecca Moritz; Berman, LaShondra; Zhang, Jing; Erdman, Dean D; Gerber, Susan I

2017-04-01

The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices. Published by Elsevier B.V.

Differential expression of miRNA-423-5p in serum from cattle challenged with bovine viral diarrhea virus

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) is an RNA virus that causes respiratory disease in cattle. MicroRNAs have been proposed as indicators of exposure to respiratory pathogens. However, microRNA profiles in cattle exposed to BVDV are currently nonexistent and few studies have been reported; therefore,...

Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia ...

Respiratory Mucosal Proteome Quantification in Human Influenza Infections.

PubMed

Marion, Tony; Elbahesh, Husni; Thomas, Paul G; DeVincenzo, John P; Webby, Richard; Schughart, Klaus

2016-01-01

Respiratory influenza virus infections represent a serious threat to human health. Underlying medical conditions and genetic make-up predispose some influenza patients to more severe forms of disease. To date, only a few studies have been performed in patients to correlate a selected group of cytokines and chemokines with influenza infection. Therefore, we evaluated the potential of a novel multiplex micro-proteomics technology, SOMAscan, to quantify proteins in the respiratory mucosa of influenza A and B infected individuals. The analysis included but was not limited to quantification of cytokines and chemokines detected in previous studies. SOMAscan quantified more than 1,000 secreted proteins in small nasal wash volumes from infected and healthy individuals. Our results illustrate the utility of micro-proteomic technology for analysis of proteins in small volumes of respiratory mucosal samples. Furthermore, when we compared nasal wash samples from influenza-infected patients with viral load ≥ 2(8) and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection.

Respiratory Mucosal Proteome Quantification in Human Influenza Infections

PubMed Central

Marion, Tony; Elbahesh, Husni; Thomas, Paul G.; DeVincenzo, John P.; Webby, Richard; Schughart, Klaus

2016-01-01

Respiratory influenza virus infections represent a serious threat to human health. Underlying medical conditions and genetic make-up predispose some influenza patients to more severe forms of disease. To date, only a few studies have been performed in patients to correlate a selected group of cytokines and chemokines with influenza infection. Therefore, we evaluated the potential of a novel multiplex micro-proteomics technology, SOMAscan, to quantify proteins in the respiratory mucosa of influenza A and B infected individuals. The analysis included but was not limited to quantification of cytokines and chemokines detected in previous studies. SOMAscan quantified more than 1,000 secreted proteins in small nasal wash volumes from infected and healthy individuals. Our results illustrate the utility of micro-proteomic technology for analysis of proteins in small volumes of respiratory mucosal samples. Furthermore, when we compared nasal wash samples from influenza-infected patients with viral load ≥ 28 and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection. PMID:27088501

Role of viral coinfections in asthma development.

PubMed

Garcia-Garcia, Maria Luz; Calvo, Cristina; Ruiz, Sara; Pozo, Francisco; Del Pozo, Victoria; Remedios, Laura; Exposito, Nadia; Tellez, Ana; Casas, Inmaculada

2017-01-01

Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections. Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis. Median current age at follow-up was 7.3 years (IQR: 6.7-8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001), and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01). Asthma at 6-8 years is more frequent and severe in those children previously hospitalized with viral

Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model.

PubMed

Otte, Anna; Marriott, Anthony C; Dreier, Carola; Dove, Brian; Mooren, Kyra; Klingen, Thorsten R; Sauter, Martina; Thompson, Katy-Anne; Bennett, Allan; Klingel, Karin; van Riel, Debby; McHardy, Alice C; Carroll, Miles W; Gabriel, Gülsah

2016-06-24

There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses.

Pneumococcal vaccination and chronic respiratory diseases.

PubMed

Froes, Filipe; Roche, Nicolas; Blasi, Francesco

2017-01-01

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

PubMed Central

Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

2016-01-01

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

Multiple Viral Infection Detected from Influenza-Like Illness Cases in Indonesia.

PubMed

Adam, Kindi; Pangesti, Krisna Nur Andriana; Setiawaty, Vivi

2017-01-01

Influenza is one of the common etiologies of the upper respiratory tract infection (URTI). However, influenza virus only contributes about 20 percent of influenza-like illness patients. The aim of the study is to investigate the other viral etiologies from ILI cases in Indonesia. Of the 334 samples, 266 samples (78%) were positive at least for one virus, including 107 (42%) cases of multiple infections. Influenza virus is the most detected virus. The most frequent combination of viruses identified was adenovirus and human rhinovirus. This recent study demonstrated high detection rate of several respiratory viruses from ILI cases in Indonesia. Further studies to determine the relationship between viruses and clinical features are needed to improve respiratory disease control program.

Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in...

Small molecules targeting viral RNA.

PubMed

Hermann, Thomas

2016-11-01

Highly conserved noncoding RNA (ncRNA) elements in viral genomes and transcripts offer new opportunities to expand the repertoire of drug targets for the development of antiinfective therapy. Ligands binding to ncRNA architectures are able to affect interactions, structural stability or conformational changes and thereby block processes essential for viral replication. Proof of concept for targeting functional RNA by small molecule inhibitors has been demonstrated for multiple viruses with RNA genomes. Strategies to identify antiviral compounds as inhibitors of ncRNA are increasingly emphasizing consideration of drug-like properties of candidate molecules emerging from screening and ligand design. Recent efforts of antiviral lead discovery for RNA targets have provided drug-like small molecules that inhibit viral replication and include inhibitors of human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe respiratory syndrome coronavirus (SARS CoV), and influenza A virus. While target selectivity remains a challenge for the discovery of useful RNA-binding compounds, a better understanding is emerging of properties that define RNA targets amenable for inhibition by small molecule ligands. Insight from successful approaches of targeting viral ncRNA in HIV, HCV, SARS CoV, and influenza A will provide a basis for the future exploration of RNA targets for therapeutic intervention in other viral pathogens which create urgent, unmet medical needs. Viruses for which targeting ncRNA components in the genome or transcripts may be promising include insect-borne flaviviruses (Dengue, Zika, and West Nile) and filoviruses (Ebola and Marburg). WIREs RNA 2016, 7:726-743. doi: 10.1002/wrna.1373 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Acute viral respiratory infections among children in MERS-endemic Riyadh, Saudi Arabia, 2012-2013.

PubMed

Fagbo, Shamsudeen F; Garbati, Musa A; Hasan, Rami; AlShahrani, Dayel; Al-Shehri, Mohamed; AlFawaz, Tariq; Hakawi, Ahmed; Wani, Tariq Ahmad; Skakni, Leila

2017-02-01

The emergence of the Middle East Respiratory Syndrome (MERS) in Saudi Arabia has intensified focus on Acute Respiratory Infections [ARIs]. This study sought to identify respiratory viruses (RVs) associated with ARIs in children presenting at a tertiary hospital. Children (aged ≤13) presenting with ARI between January 2012 and December 2013 tested for 15 RVs using the Seeplex R RV15 kit were retrospectively included. Epidemiological data was retrieved from patient records. Of the 2235 children tested, 61.5% were ≤1 year with a male: female ratio of 3:2. Viruses were detected in 1364 (61.02%) children, 233 (10.4%) having dual infections: these viruses include respiratory syncytial virus (RSV) (24%), human rhinovirus (hRV) (19.7%), adenovirus (5.7%), influenza virus (5.3%), and parainfluenzavirus-3 (4.6%). Children, aged 9-11 months, were most infected (60.9%). Lower respiratory tract infections (55.4%) were significantly more than upper respiratory tract infection (45.3%) (P < 0.001). Seasonal variation of RV was directly and inversely proportional to relative humidity and temperature, respectively, for non MERS coronaviruses (NL63, 229E, and OC43). The study confirms community-acquired RV associated with ARI in children and suggests modulating roles for abiotic factors in RV epidemiology. However, community-based studies are needed to elucidate how these factors locally influence RV epidemiology. J. Med. Virol. 89:195-201, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prevalence and seasonality of six respiratory viruses during five consecutive epidemic seasons in Belgium.

PubMed

Ramaekers, Kaat; Keyaerts, Els; Rector, Annabel; Borremans, Annie; Beuselinck, Kurt; Lagrou, Katrien; Van Ranst, Marc

2017-09-01

Acute Respiratory Infections (ARIs) are a major health problem, especially in young children and the elderly. Insights into the seasonality of respiratory viruses can help us understand when the burden on society is highest and which age groups are most vulnerable. We monitored six respiratory viruses during five consecutive seasons (2011-2016) in Belgium. Patient specimens (n=22876), tested for one or more of the following respiratory viruses, were included in this analysis: Influenza viruses (IAV & IBV), Human respiratory syncytial virus (hRSV), Human metapneumovirus (hMPV), Adenovirus (ADV) and Human parainfluenza virus (hPIV). Data were analysed for four age categories: <6y, 6-17y, 18-64y and ≥65y. Children <6y had the highest infection rates (39% positive vs. 20% positive adults) and the highest frequency of co-infections. hRSV (28%) and IAV (32%) caused the most common respiratory viral infections and followed, like hMPV, a seasonal pattern with winter peaks. hRSV followed an annual pattern with two peaks: first in young children and ±7 weeks later in elderly. This phenomenon has not been described in literature so far. hPIV and ADV occurred throughout the year with higher rates in winter. Children <6y are most vulnerable for respiratory viral infections and have a higher risk for co-infections. hRSV and IAV are the most common respiratory infections with peaks during the winter season in Belgium. Copyright © 2017 Elsevier B.V. All rights reserved.

Respiratory viruses are associated with common respiratory pathogens in cystic fibrosis.

PubMed

Esther, Charles R; Lin, Feng-Chang; Kerr, Alan; Miller, Melissa B; Gilligan, Peter H

2014-09-01

Test the hypothesis that the link between respiratory viruses and pulmonary exacerbation in cystic fibrosis (CF) reflects increased frequency or severity of lower airways infection. Molecular respiratory viral panels (RVPs), cell counts, and quantitative bacterial cultures were assessed in 235 bronchoalveolar lavage fluid (BALF) samples from 138 children with CF. Relationships among the data were analyzed using multivariate methods. RVPs were positive in 67 (28.5%) BALF samples from 52 (37.7%) patients, with rhinovirus/enterovirus most common (82.4% of RVP+). RVP+ patients were younger (5.4 years, IQR 3.0-9.7 vs. 8.0 years, IQR 3.5-12.9; P < 0.01), more likely to have respiratory symptoms (74.6% vs. 55.2%, P < 0.01), and had higher BALF percent neutrophils (70.5%, IQR 46-85% vs. 59.3%, IQR 34-77%; P < 0.05). Percent predicted FEV1 at bronchoscopy was diminished from baseline in both groups, but recovered in the RVP- (90.2 ± 22.2% vs. 89.6 ± 19.7%, P = 0.62) but not the RVP+ subjects (95.7 ± 21.1% vs. 89.1 ± 18.0%, P < 0.05). RVP status did not alter recovery rates of typical CF respiratory pathogens including Staphylococcus aureus (44.8% vs. 42.9%) and Pseudomonas aeruginosa (25.4% vs. 25.6%). However, common respiratory pathogens (Haemophilus species, Moraxella species, and Streptococcus pneumoniae) were recovered more frequently from RVP+ samples independent of age (OR 3.6, 95% CI 1.8-7.5, P < 0.001). Respiratory viruses were frequently detected in BALF from CF patients and associated with markers of disease severity. Respiratory viruses did not impact frequency or severity of infection with typical CF pathogens, but rates of infection with common respiratory pathogens were increased. This finding may have treatment implications. © 2013 Wiley Periodicals, Inc.

Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico

PubMed Central

Fernandes-Matano, Larissa; Monroy-Muñoz, Irma Eloísa; Angeles-Martínez, Javier; Sarquiz-Martinez, Brenda; Palomec-Nava, Iliana Donají; Pardavé-Alejandre, Hector Daniel; Santos Coy-Arechavaleta, Andrea; Santacruz-Tinoco, Clara Esperanza; González-Ibarra, Joaquín; González-Bonilla, Cesar Raúl

2017-01-01

Background Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. Methods This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. Results The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. Conclusion In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses. PMID:28467515

Prospects for new viral vaccines.

PubMed

Marmion, B P

1980-08-11

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

[Clinical signs of dysphagia in infants with acute viral bronchiolitis].

PubMed

Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

2014-09-01

To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study.

PubMed

García-García, María Luz; Calvo, Cristina; Rey, Cristina; Díaz, Beatriz; Molinero, Maria Del Mar; Pozo, Francisco; Casas, Inmaculada

2017-01-01

Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children's mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

PubMed

van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

2016-01-01

Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

Clinical characteristics of children with viral single- and co-infections and a petechial rash.

PubMed

Schneider, Henriette; Adams, Ortwin; Weiss, Christel; Merz, Ulrich; Schroten, Horst; Tenenbaum, Tobias

2013-05-01

Children with petechial rash are more likely to undergo invasive diagnostics, to be treated with antibiotics for potential bacterial infection and to be hospitalized. However, viruses have also been associated with petechial rash. Nonetheless, a systematic analysis of viral infections with modern available techniques as quantitative real-time polymerase chain reaction in the context of petechial rash is lacking. The purpose of this pediatric study was to prospectively uncover viral pathogens that may promote the emergence of petechiae and to analyze the correlation with the clinical characteristics and course. We conducted a prospective study in children (0 to 18 years) presenting with petechiae and signs or symptoms of infection at the emergency department between November 2009 and March 2012. In nasopharyngeal aspirates the following viruses were analyzed by quantitative real-time polymerase chain reaction: cytomegalovirus, Epstein-Barr virus, parvovirus B19, influenza A and B, parainfluenza viruses, human respiratory syncytial virus A and B, human metapneumovirus, rhinovirus, enterovirus, adenovirus, human coronavirus OC43, 229E, NL63 and human bocavirus. A viral pathogen was identified in 67% of the analyzed 58 cases with petechial rash. Virus positive patients showed a significantly higher incidence of lower respiratory tract infections. Forty-one percent were viral coinfections, which were significantly younger than virus negative patients, had a higher leukocyte count and were hospitalized for a longer time. A petechial rash is frequently associated viral single- and coinfections and can rapidly be identified via quantitative real-time polymerase chain reaction.

Climate Change and Respiratory Infections.

PubMed

Mirsaeidi, Mehdi; Motahari, Hooman; Taghizadeh Khamesi, Mojdeh; Sharifi, Arash; Campos, Michael; Schraufnagel, Dean E

2016-08-01

The rate of global warming has accelerated over the past 50 years. Increasing surface temperature is melting glaciers and raising the sea level. More flooding, droughts, hurricanes, and heat waves are being reported. Accelerated changes in climate are already affecting human health, in part by altering the epidemiology of climate-sensitive pathogens. In particular, climate change may alter the incidence and severity of respiratory infections by affecting vectors and host immune responses. Certain respiratory infections, such as avian influenza and coccidioidomycosis, are occurring in locations previously unaffected, apparently because of global warming. Young children and older adults appear to be particularly vulnerable to rapid fluctuations in ambient temperature. For example, an increase in the incidence in childhood pneumonia in Australia has been associated with sharp temperature drops from one day to the next. Extreme weather events, such as heat waves, floods, major storms, drought, and wildfires, are also believed to change the incidence of respiratory infections. An outbreak of aspergillosis among Japanese survivors of the 2011 tsunami is one such well-documented example. Changes in temperature, precipitation, relative humidity, and air pollution influence viral activity and transmission. For example, in early 2000, an outbreak of Hantavirus respiratory disease was linked to a local increase in the rodent population, which in turn was attributed to a two- to threefold increase in rainfall before the outbreak. Climate-sensitive respiratory pathogens present challenges to respiratory health that may be far greater in the foreseeable future.

Zoonotic viral diseases and the frontier of early diagnosis, control and prevention.

PubMed

Heeney, J L

2006-11-01

Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human-to-human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.

Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

This study investigated viruses in bovine respiratory disease (BRD) cases in feedlots, including bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). Nasal swabs were collected fro...

Glycomic Characterization of Respiratory Tract Tissues of Ferrets

PubMed Central

Jia, Nan; Barclay, Wendy S.; Roberts, Kim; Yen, Hui-Ling; Chan, Renee W. Y.; Lam, Alfred K. Y.; Air, Gillian; Peiris, J. S. Malik; Dell, Anne; Nicholls, John M.; Haslam, Stuart M.

2014-01-01

The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2–3- or α2–6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2–3 binding being associated with avian influenza viruses and α2–6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2–3- and α2–6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1–4)Galβ1–4GlcNAc) and sialylated N,N′-diacetyllactosamine (NeuAcα2–6GalNAcβ1–4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection. PMID:25135641

Efficacy of a homeopathic complex on acute viral tonsillitis.

PubMed

Malapane, Eunice; Solomon, Elizabeth M; Pellow, Janice

2014-11-01

Acute viral tonsillitis is an upper respiratory tract infection prevalent in school-aged children. Because this condition is self-limiting, conventional treatment options are usually palliative. Homeopathic remedies are a useful alternative to conventional medications in acute uncomplicated upper respiratory tract infections in children, offering earlier symptom resolution, cost-effectiveness, and fewer adverse effects. This study aimed to determine the efficacy of a homeopathic complex on the symptoms of acute viral tonsillitis in African children in South Africa. This was a randomized, double-blind, placebo-controlled, 6-day pilot study. Thirty children, age 6 to 12 years, with acute viral tonsillitis were recruited from a primary school in Gauteng, South Africa. Participants took two tablets of the medication four times daily. The treatment group received lactose tablets medicated with the homeopathic complex (Atropa belladonna D4, Calcarea phosphoricum D4, Hepar sulphuris D4, Kalium bichromat D4, Kalium muriaticum D4, Mercurius protoiodid D10, and Mercurius biniodid D10). The placebo consisted of the unmedicated vehicle only. The Wong-Baker FACES Pain Rating Scale measured pain intensity, and a Symptom Grading Scale assessed changes in tonsillitis signs and symptoms. The treatment group had a statistically significant improvement in the following symptoms compared with the placebo group: pain associated with tonsillitis, pain on swallowing, erythema and inflammation of the pharynx, and tonsil size. The homeopathic complex used in this study exhibited significant anti-inflammatory and pain-relieving qualities in children with acute viral tonsillitis. No patients reported any adverse effects. These preliminary findings are promising; however, the sample size was small and therefore a definitive conclusion cannot be reached. A larger, more inclusive research study should be undertaken to verify the findings of this study.

Viral infection of the lungs through the eye.

PubMed

Bitko, Vira; Musiyenko, Alla; Barik, Sailen

2007-01-01

Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.

Successful topical respiratory tract immunization of primates against Ebola virus.

PubMed

Bukreyev, Alexander; Rollin, Pierre E; Tate, Mallory K; Yang, Lijuan; Zaki, Sherif R; Shieh, Wun-Ju; Murphy, Brian R; Collins, Peter L; Sanchez, Anthony

2007-06-01

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

Nosocomial Transmission of Respiratory Syncytial Virus in an Outpatient Cancer Center

PubMed Central

Chu, Helen Y.; Englund, Janet A.; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P.; Boeckh, Michael; Pergam, Steven A.; Casper, Crey

2014-01-01

Background Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. Methods We performed a retrospective cohort study of two nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance (SCCA). Subjects included patients seen at the SCCA with RSV detected in two outbreaks in 2007-2008 and 2012, and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested polymerase chain reaction targeting the RSV attachment glycoprotein coding region. Results Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 (67%) of 15 patients with RSV sequenced from 2007-2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; nine (90%) of 10 patients had the same viral strain, and 1 (10%) had another viral strain. Conclusions We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. PMID:24607551

Coronavirus infection in intensively managed cattle with respiratory disease.

PubMed

Hick, P M; Read, A J; Lugton, I; Busfield, F; Dawood, K E; Gabor, L; Hornitzky, M; Kirkland, P D

2012-10-01

A detailed laboratory investigation identified bovine coronavirus (BCoV) as the aetiological agent in an outbreak of respiratory disease at a semi-intensive beef cattle feedlot in south-east Australia. The outbreak caused 30% morbidity in the resident population and also affected two cohorts of cattle that were newly introduced to the property. At slaughter, pulmonary consolidation and inflammatory lesions in the trachea were identified in 15 of 49 animals. Pasteurella multocida or Histophilus somni was cultured from 3 of 7 animals with lesions. Histopathological examination revealed multifocal non-suppurative bronchointerstitial pneumonia with formation of epithelial syncytial cells, sometimes associated with suppurative bronchopneumonia. BCoV was detected in nasal swabs and pulmonary lesions using real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay and virus isolation. There was serological evidence of previous exposure to bovine viral diarrhoea virus, bovine respiratory syncytial virus and bovine parainfluenza virus type 3, but not to bovine herpesvirus type 1. None of these viral pathogens or Mycoplasma bovis was identified by qRT-PCR. This is believed to be the first report of BCoV in association with bovine respiratory disease complex in Australia. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Phosphorylation of the human respiratory syncytial virus P protein mediates M2-2 regulation of viral RNA synthesis, a process that involves two P proteins.

PubMed

Asenjo, Ana; Villanueva, Nieves

2016-01-04

The M2-2 protein regulates the balance between human respiratory syncytial virus (HRSV) transcription and replication. Here it is shown that M2-2 mediated transcriptional inhibition is managed through P protein phosphorylation. Transcription inhibition by M2-2 of the HRSV based minigenome pRSVluc, required P protein phosphorylation at serines (S) in positions 116, 117, 119 and increased inhibition is observed if S232 or S237 is also phosphorylated. Phosphorylation of these residues is required for viral particle egression from infected cells. Viral RNA synthesis complementation assays between P protein variants, suggest that two types of P proteins participate in the process as components of RNA dependent RNA polymerase (RdRp). Type I is only functional when, as a homotetramer, it is bound to N and L proteins through residues 203-241. Type II is functionally independent of these interactions and binds to N protein at a region outside residues 232-241. P protein type I phosphorylation at S116, S117 and S119, did not affect the activity of RdRp but this phosphorylation in type II avoids its interaction with N protein and impairs RdRp functionality for transcription and replication. Structural changes in the RdRp, mediated by phosphorylation turnover at the indicated residues, in the two types of P proteins, may result in a fine adjustment, late in the infectious cycle, of transcription, replication and progression in the morphogenetic process that ends in egression of the viral particles from infected cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Shared Bacterial and Viral Respiratory Agents in Bighorn Sheep (Ovis canadensis), Domestic Sheep (Ovis aries), and Goats (Capra hircus) in Montana

PubMed Central

Miller, David S.; Weiser, Glen C.; Aune, Keith; Roeder, Brent; Atkinson, Mark; Anderson, Neil; Roffe, Thomas J.; Keating, Kim A.; Chapman, Phillip L.; Kimberling, Cleon; Rhyan, Jack; Clarke, P. Ryan

2011-01-01

Transmission of infectious agents from livestock reservoirs has been hypothesized to cause respiratory disease outbreaks in bighorn sheep (Ovis canadensis), and land management policies intended to limit this transmission have proven controversial. This cross-sectional study compares the infectious agents present in multiple populations of bighorn sheep near to and distant from their interface with domestic sheep (O. aries) and domestic goat (Capra hircus) and provides critical baseline information needed for interpretations of cross-species transmission risks. Bighorn sheep and livestock shared exposure to Pasteurellaceae, viral, and endoparasite agents. In contrast, although the impact is uncertain, Mycoplasma sp. was isolated from livestock but not bighorn sheep. These results may be the result of historic cross-species transmission of agents that has resulted in a mosaic of endemic and exotic agents. Future work using longitudinal and multiple population comparisons is needed to rigorously establish the risk of outbreaks from cross-species transmission of infectious agents. PMID:22195293

Shared Bacterial and Viral Respiratory Agents in Bighorn Sheep (Ovis canadensis), Domestic Sheep (Ovis aries), and Goats (Capra hircus) in Montana.

PubMed

Miller, David S; Weiser, Glen C; Aune, Keith; Roeder, Brent; Atkinson, Mark; Anderson, Neil; Roffe, Thomas J; Keating, Kim A; Chapman, Phillip L; Kimberling, Cleon; Rhyan, Jack; Clarke, P Ryan

2011-01-01

Transmission of infectious agents from livestock reservoirs has been hypothesized to cause respiratory disease outbreaks in bighorn sheep (Ovis canadensis), and land management policies intended to limit this transmission have proven controversial. This cross-sectional study compares the infectious agents present in multiple populations of bighorn sheep near to and distant from their interface with domestic sheep (O. aries) and domestic goat (Capra hircus) and provides critical baseline information needed for interpretations of cross-species transmission risks. Bighorn sheep and livestock shared exposure to Pasteurellaceae, viral, and endoparasite agents. In contrast, although the impact is uncertain, Mycoplasma sp. was isolated from livestock but not bighorn sheep. These results may be the result of historic cross-species transmission of agents that has resulted in a mosaic of endemic and exotic agents. Future work using longitudinal and multiple population comparisons is needed to rigorously establish the risk of outbreaks from cross-species transmission of infectious agents.

Shared bacterial and viral respiratory agents in bighorn sheep (Ovis canadensis), domestic sheep (Ovis aries), and goats (Capra hircus) in Montana

USGS Publications Warehouse

Miller, David S.; Weiser, Glen C.; Aune, Keith; Roeder, Brent; Atkinson, Mark; Anderson, Neil; Roffe, Thomas J.; Keating, Kim A.; Chapman, Phillip L.; Kimberling, Cleon; Rhyan, Jack C.; Clarke, P. Ryan

2011-01-01

Transmission of infectious agents from livestock reservoirs has been hypothesized to cause respiratory disease outbreaks in bighorn sheep (Ovis canadensis), and land management policies intended to limit this transmission have proven controversial. This cross-sectional study compares the infectious agents present in multiple populations of bighorn sheep near to and distant from their interface with domestic sheep (O. aries) and domestic goat (Capra hircus) and provides critical baseline information needed for interpretations of cross-species transmission risks. Bighorn sheep and livestock shared exposure to Pasteurellaceae, viral, and endoparasite agents. In contrast, although the impact is uncertain, Mycoplasma sp. was isolated from livestock but not bighorn sheep. These results may be the result of historic cross-species transmission of agents that has resulted in a mosaic of endemic and exotic agents. Future work using longitudinal and multiple population comparisons is needed to rigorously establish the risk of outbreaks from cross-species transmission of infectious agents.

Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital.

PubMed

Teh, Benjamin W; Worth, Leon J; Harrison, Simon J; Thursky, Karin A; Slavin, Monica A

2015-07-01

Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.

Evaluation of the PrimerDesign™ genesig real-time reverse transcription-polymerase chain reaction assay and the INFINITI® Respiratory Viral Panel Plus assay for the detection of human metapneumovirus in Kuwait.

PubMed

Al-Turab, Mariam; Chehadeh, Wassim; Al-Mulla, Fahd; Al-Nakib, Widad

2012-04-01

Human metapneumovirus (hMPV) is a respiratory pathogen that was discovered in 2001 and is considered a major cause of both upper and lower respiratory tract infections. A sensitive, fast, and high-throughput diagnostic test is needed for the detection of hMPV that may assist in the clinical management as well as in the reduction of inappropriate therapy. Therefore, a comparison assessment was performed in this study between the PrimerDesign™ genesig real-time reverse transcription-polymerase chain reaction (RT-PCR) Assay and the INFINITI(®) Respiratory Viral Panel Plus Assay (RVP-Plus) for the detection of hMPV infection in patients with respiratory tract infections. A total of 200 respiratory samples were collected from 185 hospitalized patients, during the winter season in Kuwait. Of 185 patients, 10 (5.4%) were positive for hMPV RNA by the in-house RT-PCR assay, while 7 (4%) were positive for hMPV RNA by the real-time RT-PCR assay and 9 (5%) were positive for hMPV RNA by the INFINITI(®) RVP-Plus assay. The high incidence rate (60%) of hMPV infection was in January 2011. The sensitivity of the real-time RT-PCR and INFINITI(®) RVP-Plus assays was 70% and 90%, respectively, with specificity of 100% for both assays. hMPV types A and B could be identified in this study; however, discordant genotyping results were found between the direct sequencing method and the INFINITI(®) RVP-Plus assay in 33% of hMPV-positive patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Etiology of respiratory disease in non-vaccinated, non-medicated calves in rearing herds.

PubMed

Autio, T; Pohjanvirta, T; Holopainen, R; Rikula, U; Pentikäinen, J; Huovilainen, A; Rusanen, H; Soveri, T; Sihvonen, L; Pelkonen, S

2007-01-31

The aim of this study was to examine the occurrence of bacterial, mycoplasmal and viral pathogens in the lower respiratory tract of calves in all-in all-out calf-rearing units. According to clinical status, non-medicated calves with and without respiratory disease signs were selected of the 40 herds investigated to analyse the micro-organisms present in healthy and diseased calves. Tracheobronchial lavage (TBL) and paired serum samples were analysed for bacteria, mycoplasmas, respiratory syncytial virus (RSV), parainfluenza virus 3 (PIV3), bovine corona virus (BCV) and bovine adenovirus (BAV). Pasteurella multocida was the most common bacterial pathogen. It was isolated from 34% of the TBL samples in 28 herds and was associated with clinical respiratory disease (p < 0.05) when other pathogenic bacteria or mycoplasma were present in the sample. Mannheimia spp. and Histophilus somni were rarely found. Mycoplasma bovis was not detected at all. Ureaplasma diversum was associated with clinical respiratory disease (p < 0.05). TBL samples from healthy or suspect calves were more often negative in bacterial culture than samples from diseased calves (p < 0.05). No viral infections were detected in six herds, while 16-21 herds had RSV, BCV, BAV or PIV3. In the herds that had calves seroconverted to BCV, respiratory shedding of BCV was more frequently observed than faecal shedding. This study showed that the microbial combinations behind BRD were diverse between herds. M. bovis, an emerging pathogen in many countries, was not detected.

Is there a genetic solution to bovine respiratory disease complex?

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a complex multi-factor disease, which increases costs and reduces revenue from feedlot cattle. Multiple stressors and pathogens (viral and bacterial) have been implicated in the etiology of BRDC, therefore multiple approaches will be needed to evaluate a...

The Naval Health Research Center Respiratory Disease Laboratory.

PubMed

Ryan, M; Gray, G; Hawksworth, A; Malasig, M; Hudspeth, M; Poddar, S

2000-07-01

Concern about emerging and reemerging respiratory pathogens prompted the development of a respiratory disease reference laboratory at the Naval Health Research Center. Professionals working in this laboratory have instituted population-based surveillance for pathogens that affect military trainees and responded to threats of increased respiratory disease among high-risk military groups. Capabilities of this laboratory that are unique within the Department of Defense include adenovirus testing by viral shell culture and microneutralization serotyping, influenza culture and hemagglutination inhibition serotyping, and other special testing for Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumonia, and Chlamydia pneumoniae. Projected capabilities of this laboratory include more advanced testing for these pathogens and testing for other emerging pathogens, including Bordetella pertussis, Legionella pneumoniae, and Haemophilus influenzae type B. Such capabilities make the laboratory a valuable resource for military public health.

Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox

PubMed Central

Parker, Scott; Chen, Nanhai G.; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E.; Schriewer, Jill; Buller, R. Mark

2013-01-01

The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analogue of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is 4 or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection – thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. PMID:22381921

Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.

PubMed

Parker, Scott; Chen, Nanhai G; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E; Schriewer, Jill; Mark Buller, R

2012-04-01

The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Copyright © 2012 Elsevier B.V. All rights reserved.

Fatal Canid Herpesvirus 1 Respiratory Infections in 4 Clinically Healthy Adult Dogs.

PubMed

Kumar, S; Driskell, E A; Cooley, A J; Jia, K; Blackmon, S; Wan, X-F; Uhl, E W; Saliki, J T; Sanchez, S; Krimer, P M; Hogan, R J

2015-07-01

Four healthy adult dogs (Golden Retrievers aged 6 years and 9 years, Dalmatian aged 13 years, and Mastiff aged 5 years) developed clinical signs of acute respiratory disease and died within 2 to 7 days of onset of clinical signs. The lungs of the 3 dogs submitted for necropsy were diffusely and severely reddened due to hyperemia and hemorrhage. Microscopic lesions in all dogs were suggestive of acute viral or toxic respiratory damage and varied from acute severe fibrinonecrotic or hemorrhagic bronchopneumonia to fibrinous or necrotizing bronchointerstitial pneumonia. Necropsied dogs also had hemorrhagic rhinitis and tracheitis with necrosis. Virus isolation, transmission electron microscopy, and polymerase chain reaction were used to confirm the presence of canid herpesvirus 1 (CaHV-1) in the lung samples of these dogs. Lung tissues were negative for influenza A virus, canine distemper virus, canine parainfluenza virus, canine respiratory coronavirus, and canine adenovirus 2. Canid herpesvirus 1 has been isolated from cases of acute infectious respiratory disease in dogs but has only rarely been associated with fatal primary viral pneumonia in adult dogs. The cases in the current report document lesions observed in association with CaHV-1 in 4 cases of fatal canine herpesvirus pneumonia in adult dogs. © The Author(s) 2014.

Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease.

PubMed

Douglas, Madeline G; Kocher, Jacob F; Scobey, Trevor; Baric, Ralph S; Cockrell, Adam S

2018-04-01

We recently established a mouse model (288-330 +/+ ) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10 6 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10 3 and 10 5 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10-1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study.

PubMed

Arabi, Yaseen M; Al-Omari, Awad; Mandourah, Yasser; Al-Hameed, Fahad; Sindi, Anees A; Alraddadi, Basem; Shalhoub, Sarah; Almotairi, Abdullah; Al Khatib, Kasim; Abdulmomen, Ahmed; Qushmaq, Ismael; Mady, Ahmed; Solaiman, Othman; Al-Aithan, Abdulsalam M; Al-Raddadi, Rajaa; Ragab, Ahmed; Al Mekhlafi, Ghaleb A; Al Harthy, Abdulrahman; Kharaba, Ayman; Ahmadi, Mashael Al; Sadat, Musharaf; Mutairi, Hanan Al; Qasim, Eman Al; Jose, Jesna; Nasim, Maliha; Al-Dawood, Abdulaziz; Merson, Laura; Fowler, Robert; Hayden, Frederick G; Balkhy, Hanan H

2017-10-01

To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. Retrospective cohort study. Patients admitted to ICUs in 14 Saudi Arabian hospitals. Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). None. Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non-Middle East respiratory syndrome severe acute respiratory

Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010-2011.

PubMed

Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

2014-06-01

The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥ 2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2-17 years, whereas other viruses had varied patterns among age groups. The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.

Protective effect of surfactant protein d in pulmonary vaccinia virus infection: implication of A27 viral protein.

PubMed

Perino, Julien; Thielens, Nicole M; Crouch, Erika; Spehner, Danièle; Crance, Jean-Marc; Favier, Anne-Laure

2013-03-21

Vaccinia virus (VACV) was used as a surrogate of variola virus (VARV) (genus Orthopoxvirus), the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D), constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/-) resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27.

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

PubMed

See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

2008-09-01

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

Nosocomial transmission of respiratory syncytial virus in an outpatient cancer center.

PubMed

Chu, Helen Y; Englund, Janet A; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P; Boeckh, Michael; Pergam, Steven A; Casper, Corey

2014-06-01

Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. We performed a retrospective cohort study of 2 nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance. Subjects included patients seen at the Seattle Cancer Care Alliance with RSV detected in 2 outbreaks in 2007-2008 and 2012 and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested PCR targeting the RSV attachment glycoprotein coding region. Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 of 15 patients (67%) with RSV sequenced from 2007 to 2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; 9 of 10 patients (90%) had the same viral strain, and 1 (10%) had another viral strain. We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.

Respiratory Tract Infections and Voice Quality in 4-Year-old Children in the STEPS Study.

PubMed

Kallvik, Emma; Toivonen, Laura; Peltola, Ville; Kaljonen, Anne; Simberg, Susanna

2018-03-02

Health-related factors are part of the multifactorial background of dysphonia in children. Respiratory tract infections affect the same systems and structures that are used for voice production. The purpose of this study was to investigate if the number of respiratory tract infections or the viral etiology were significant predictors for a more hoarse voice quality. The participants were 4-year-old children who participated in the multidisciplinary STEPS study (Steps to the Healthy Development and Well-being of Children) where they were followed up from pregnancy or birth to 4 years of age. Data were collected through questionnaires and a health diary filled in by the parents. Some of the children were followed up more intensively for respiratory tract infections during the first 2 years of life, and nasal swab samples were taken at the onset of respiratory symptoms. Our participants were 489 of these children who had participated in the follow-up for at least 1 year and for whom data on respiratory tract infections and data on voice quality were available. The number of hospitalizations due to respiratory tract infections was a significant predictor for a more hoarse voice quality. Neither the number of rhinovirus infections nor the number of respiratory syncytial virus infections was statistically significant predictors for a more hoarse voice quality. Based on our results, we would suggest including questions on the presence of respiratory tract infections that have led to hospitalization in the pediatric voice anamnesis. Whether the viral etiology of respiratory tract infections is of importance or not requires further research. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Adenovirus Respiratory Tract Infections in Peru

PubMed Central

Ampuero, Julia S.; Ocaña, Víctor; Gómez, Jorge; Gamero, María E.; Garcia, Josefina; Halsey, Eric S.; Laguna-Torres, V. Alberto

2012-01-01

Background Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. Methods/Principal Findings Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. Conclusions/Significance HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness. PMID:23056519

Pathophysiology of viral-induced exacerbations of COPD

PubMed Central

Alfredo, Potena; Gaetano, Caramori; Paolo, Casolari; Marco, Contoli; Johnston, Sebastian L; Alberto, Papi

2007-01-01

Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation. PMID:18268922

Viruses Associated With Acute Respiratory Infections and Influenza-like Illness Among Outpatients From the Influenza Incidence Surveillance Project, 2010–2011

PubMed Central

Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

2017-01-01

Background The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. Methods From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. Results The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. Conclusions The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children. PMID:24338352

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness

PubMed Central

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-01-01

Rationale Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Objective Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. Setting 6 major hospitals in 2 districts of Beijing, China. Design Cluster randomised controlled trial. Participants 245 index cases with ILI. Intervention Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Main outcome measure Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. Results In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. Conclusions The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. Trial registration number ACTRN12613000852752; Results. PMID:28039289

Respiratory and intraperitoneal infection of mice with encephalomyocarditis virus: effect of sublethal x-irradiation on host resistance and survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogaerts, W.J.C.; Durville-vanderoord, B.J.

1975-01-01

The relationships governing host resistance to viral infection were evaluated in mice following respiratory or peritoneal infection with three strains of encephalomyocarditis (EMC) virus, which were antigenically similar but differed in virulence. Host resistance to each strain was evaluated by determining the mean lethal dose LD50, and the mean infectious dose ID50. The contribution of non-specific resistance to the overall defense of the host was assessed in mice that had received 450 R of x irradiation prior to viral infection. Experimental results indicate that host capacity to resist respiratory infection exceeds that for peritoneal infection for the three EMC strains.more » It is concluded that respiratory inoculation of virus affords better immunization against EMC virus infection than does peritoneal infection. (Author) (GRA)« less

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

PubMed Central

Liu, Guangliang; Wang, Ruixue; London, Steven D.; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 107 pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation. PMID:23437361

Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

PubMed

Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

Surveillance of Severe Acute Respiratory Infection (SARI) for Hospitalized Patients in Northern Vietnam, 2011-2014.

PubMed

Nguyen, Hang Khanh Le; Nguyen, Son Vu; Nguyen, Anh Phuong; Hoang, Phuong Mai Vu; Le, Thanh Thi; Nguyen, Thach Co; Hoang, Huong Thu; Vuong, Cuong Duc; Tran, Loan Thi Thanh; Le, Mai Quynh

2017-09-25

Severe acute respiratory infections (SARI) are leading causes of hospitalization, morbidity, and mortality in children worldwide. The aim of this study was to identify viral pathogens responsible for SARI in northern Vietnam in the period from 2011 to 2014. Throat swabs and tracheal aspirates were collected from SARI patients according to WHO guidelines. The presence of 13 different viral pathogens (influenza A[H1N1]pdm09; A/H3N2; A/H5; A/H7 and B; para influenza 1,2,3; RSV; HMPV; adeno; severe acute respiratory syndrome-CoV and rhino) was tested by conventional/real-time reverse transcription-polymerase chain reaction. During the study period, 975 samples were collected and tested. More than 30% (32.1%, 313 samples) of the samples showed evidence of infection with influenza viruses, including A/H3N2 (48 samples), A (H1N1) pdm09 (221 samples), influenza B (42 samples), and co-infection of A (H1N1) pdm09 or A/H3N2 and influenza B (2 samples). Other respiratory pathogens were detected in 101 samples, including rhinovirus (73 samples), adenovirus (10 samples), hMPV (9 samples), parainfluenza 3 (5 samples), parainfluenza 2 (3 samples), and RSV (1 sample). Influenza A/H5, A/H7, or SARS-CoV were not detected. Respiratory viral infection, particularly infection of influenza and rhinoviruses, were associated with high rates of SARI hospitalization, and future studies correlating the clinical aspects are needed to design interventions, including targeted vaccination.

Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates.

PubMed

Li, Yan; Khalafalla, Abdelmalik Ibrahim; Paden, Clinton R; Yusof, Mohammed F; Eltahir, Yassir M; Al Hammadi, Zulaikha M; Tao, Ying; Queen, Krista; Hosani, Farida Al; Gerber, Susan I; Hall, Aron J; Al Muhairi, Salama; Tong, Suxiang

2017-01-01

Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population.

Nation-wide surveillance of human acute respiratory virus infections between 2013 and 2015 in Korea.

PubMed

Kim, Jeong-Min; Jung, Hee-Dong; Cheong, Hyang-Min; Lee, Anna; Lee, Nam-Joo; Chu, Hyuk; Lee, Joo-Yeon; Kim, Sung Soon; Choi, Jang-Hoon

2018-07-01

The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36 915 patients with ARIs, and viral nucleic acids were detected by real-time (reverse-transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV). The overall positive rate of patient specimens was 49.4% (18 236/36 915), 5% of which carried two or more viruses simultaneously. HRV (15.6%) was the most predominantly detected virus, followed by IFVs (14.6%), HAdV (7.5%), HPIVs (5.8%), HCoVs (4.2%), HRSVs (3.6%), HBoV (1.9%), and HMPV (1.6%). Most of the ARIs were significantly correlated with clinical symptoms of fever, cough, and runny nose. Although HRV and HAdV were frequently detected throughout the year in patients, other respiratory viruses showed apparent seasonality. HRSVs and IFVs were the major causative agents of acute respiratory diseases in infants and young children. Overall, this study demonstrates a meaningful relationship between viral infection and typical manifestations of known clinical features as well as seasonality, age distribution, and co-infection among respiratory viruses. Therefore, these data could provide useful information for public health management and to enhance patient care for primary clinicians. © 2018 Wiley Periodicals, Inc.

Respiratory inflammation and infections in high-performance athletes.

PubMed

Gleeson, Maree; Pyne, David B

2016-02-01

Upper respiratory illness is the most common reason for non-injury-related presentation to a sports medicine clinic, accounting for 35-65% of illness presentations. Recurrent or persistent respiratory illness can have a negative impact on health and performance of athletes undertaking high levels of strenuous exercise. The cause of upper respiratory symptoms (URS) in athletes can be uncertain but the majority of cases are related to common respiratory viruses, viral reactivation, allergic responses to aeroallergens and exercise-related trauma to the integrity of respiratory epithelial membranes. Bacterial respiratory infections are uncommon in athletes. Undiagnosed or inappropriately treated asthma and/or allergy are common findings in clinical assessments of elite athletes experiencing recurrent URS. High-performance athletes with recurrent episodes of URS should undergo a thorough clinical assessment to exclude underlying treatable conditions of respiratory inflammation. Identifying athletes at risk of recurrent URS is important in order to prescribe preventative clinical, training and lifestyle strategies. Monitoring secretion rates and falling concentrations of salivary IgA can identify athletes at risk of URS. Therapeutic interventions are limited by the uncertainty of the underlying cause of inflammation. Topical anti-inflammatory sprays can be beneficial for some athletes. Dietary supplementation with bovine colostrum, probiotics and selected antioxidants can reduce the incidence or severity of URS in some athletes. Preliminary studies on athletes prone to URS indicate a genetic predisposition to a pro-inflammatory response and a dysregulated anti-inflammatory cytokine response to intense exercise as a possible mechanism of respiratory inflammation. This review focuses on respiratory infections and inflammation in elite/professional athletes.

Mechanisms of infection in the respiratory tract.

PubMed

Baskerville, A

1981-12-01

Related to its potential vulnerability the respiratory tract has a very complex and effective defence apparatus. The interaction between these defence mechanisms and certain characteristics of aetiological agents results in a pattern in which initial infections by these agents tend to occur at specific sites in the tract. Infections in which the primary portal of entry is in the upper respiratory tract include Bordetella bronchiseptica and Haemophilus spp in pigs; Pasteurella spp in cattle, sheep, pigs; Mycoplasma spp in cattle, sheep, pigs and poultry; equine herpesvirus 1 in horses; infectious bovine rhinotracheitis in cattle; parainfluenza 3 in cattle and sheep; infectious laryngo-tracheitis and infectious bronchitis in poultry; feline viral rhinotracheitis and calicivirus in cats; Aujeszky's disease virus and swine influenza in pigs; and equine influenza in horses. Infections in which the primary portal of entry is in the lower respiratory tract include Aspergillus fumigatus in poultry and mammals, respiratory syncytial virus in cattle, distemper virus in dogs and adenovirus in cattle and dogs. A fuller understanding of the interactions between an agent and the host at the point of entry would make it much easier to develop effective vaccines and therapeutic agents.

Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia.

PubMed

Kim, Ho-Cheol; Choi, Sang-Ho; Huh, Jin-Won; Sung, Heungsup; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

2016-12-01

Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus–Methicillin-Resistant S. aureus Coinfection in Children

PubMed Central

Yu, Karl O. A.; Randolph, Adrienne G.; Agan, Anna A.; Yip, Wai-Ki; Truemper, Edward J.; Weiss, Scott L.; Ackerman, Kate G.; Schwarz, Adam J.; Giuliano, John S.; Hall, Mark W.; Bubeck Wardenburg, Juliane

2016-01-01

Background. Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral coinfection is unclear. Methods. We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model. Results. Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-toxin–specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia. Conclusions. These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy. PMID:27651418

Association between nasopharyngeal load of Streptococcus pneumoniae, viral coinfection, and radiologically confirmed pneumonia in Vietnamese children.

PubMed

Vu, Huong Thi Thu; Yoshida, Lay Myint; Suzuki, Motoi; Nguyen, Hien Anh Thi; Nguyen, Cat Dinh Lien; Nguyen, Ai Thi Thuy; Oishi, Kengo; Yamamoto, Takeshi; Watanabe, Kiwao; Vu, Thiem Dinh

2011-01-01

The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia children with viral coinfection compared with those children without viral coinfection (1.4 x 10⁷/mL vs. 9.1 x 10⁵/mL; P 0.0001). SP load was over 200-fold higher in serotypeable SP compared with nontypeable SP (2.5 x 10⁶/mL vs. 1 x 10⁴/mL; P < 0.0001). These associations were independent of potential confounders in multiple regression models. No clear association was found between nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral coinfection in either RCP or other LRTIs groups. An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.

Probiotics to Prevent Respiratory Infections in Nursing Homes: A Pilot Randomized Controlled Trial.

PubMed

Wang, Biao; Hylwka, Tammy; Smieja, Marek; Surrette, Michael; Bowdish, Dawn M E; Loeb, Mark

2018-05-09

To assess the feasibility of conducting a large clinical trial to evaluate the effectiveness of probiotics to reduce influenza and other respiratory virus infections in residents of long-term and chronic care facilities (LTCFs). Randomized, double-blind, placebo-controlled pilot trial. Fourteen nursing homes in Hamilton and surrounding region, Ontario, Canada. Nursing home residents aged 65 and older (N=209). Those who were taking immunosuppressives (steroids or other immunosuppressives) or had a hematological malignancy, structural heart disease, or gastroesophageal or intestinal injury and others at high risk of an endovascular infection were excluded. Participants were randomized to receive study probiotics-2 capsules of Lactobacillus rhamnosus GG (estimated 10 billion colony forming units of L. rhamnosus GG per capsule) or placebo (calcium carbonate) daily for 6 months. Laboratory-confirmed respiratory viral infections. One hundred ninety-six individuals were included in the analysis: 100 in the probiotics group and 96 in the placebo group. Laboratory-confirmed respiratory viral infections were observed in 14 (15.0%) residents in the probiotic group and 21 (22.9%) in the placebo group (hazard ratio=0.65, 95% confidence interval=0.32-1.31). A larger trial is warranted to determine whether probiotics reduce influenza and other respiratory virus infections in residents of LTCFs. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

The CD8 T Cell Response to Respiratory Virus Infections.

PubMed

Schmidt, Megan E; Varga, Steven M

2018-01-01

Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.

ACUTE LOWER RESPIRATORY INFECTION IN GUARANI INDIGENOUS CHILDREN, BRAZIL.

PubMed

Souza, Patricia Gomes de; Cardoso, Andrey Moreira; Sant'Anna, Clemax Couto; March, Maria de Fátima Bazhuni Pombo

2018-03-29

To describe the clinical profile and treatment of Brazilian Guarani indigenous children aged less than five years hospitalized for acute lower respiratory infection (ALRI), living in villages in the states from Rio de Janeiro to Rio Grande do Sul. Of the 234 children, 23 were excluded (incomplete data). The analysis was conducted in 211 children. Data were extracted from charts by a form. Based on record of wheezing and x-ray findings, ALRI was classified as bacterial, viral and viral-bacterial. A bivariate analysis was conducted using multinomial regression. Median age was 11 months. From the total sample, the ALRI cases were classified as viral (40.8%), bacterial (35.1%) and viral-bacterial (24.1%). It was verified that 53.1% of hospitalizations did not have clinical-radiological-laboratorial evidence to justify them. In the multinomial regression analysis, the comparison of bacterial and viral-bacterial showed the likelihood of having a cough was 3.1 times higher in the former (95%CI 1.11-8.70), whereas having chest retractions was 61.0% lower (OR 0.39, 95%CI 0.16-0.92). Comparing viral with viral-bacterial, the likelihood of being male was 2.2 times higher in the viral (95%CI 1.05-4.69), and of having tachypnea 58.0% lower (OR 0.42, 95%CI 0.19-0.92). Higher proportion of viral processes was identified, as well as viral-bacterial co-infections. Coughing was a symptom indicative of bacterial infection, whereas chest retractions and tachypnea showed viral-bacterial ALRI. Part of the resolution of non-severe ALRI still occurs at hospital level; therefore, we concluded that health services need to implement their programs in order to improve indigenous primary care.

Influenza and other respiratory viruses in three Central American countries

PubMed Central

Laguna‐Torres, Victor A.; Sánchez‐Largaespada, José F.; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E.; Halsey, Eric S.; Kochel, Tadeusz J.

2010-01-01

Please cite this paper as: Laguna‐Torres et al. (2011) Influenza and other respiratory viruses in three Central American countries. Influenza and Other Respiratory Viruses 5(2), 123–134. Background  Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. Aims  To analyze viral etiologic agents associated with influenza‐like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Methods  Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. Results  A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. Discussion  When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Conclusion  Genetic analysis of influenza

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

PubMed Central

Siemens, Nikolai; Oehmcke-Hecht, Sonja; Mettenleiter, Thomas C.; Kreikemeyer, Bernd; Valentin-Weigand, Peter; Hammerschmidt, Sven

2017-01-01

Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health. PMID:29312268

Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs.

PubMed

Mora, Alejandro Larios; Detalle, Laurent; Gallup, Jack M; Van Geelen, Albert; Stohr, Thomas; Duprez, Linde; Ackermann, Mark R

2018-05-07

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined: day 1-5 or day 3-5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.

The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation.

PubMed

Etherington, C; Naseer, R; Conway, S P; Whitaker, P; Denton, M; Peckham, D G

2014-01-01

Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

PubMed Central

Larcombe, Alexander N.; Foong, Rachel E.; Boylen, Catherine E.; Zosky, Graeme R.

2012-01-01

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background  Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives  To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods  We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results  Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions  A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice. PMID:22994877

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

2008-01-01

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Detection of Respiratory Viruses in Sputum from Adults by Use of Automated Multiplex PCR

PubMed Central

Walsh, Edward E.; Formica, Maria A.; Falsey, Ann R.

2014-01-01

Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on “dunked” sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone. PMID:25056335

Yeast supplementation altered the metabolic response to a combined viral-bacterial challenge in feedlot heifers

USDA-ARS?s Scientific Manuscript database

Two treatments were evaluated in feedlot heifers to determine the effects of feeding a yeast supplement on metabolic responses to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (325 +/- 19.2 kg) were selected and randomly assigned to one of two treatments: 1) Contr...

Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates

PubMed Central

Eltahir, Yassir M.; Al Hammadi, Zulaikha M.; Tao, Ying; Queen, Krista; Hosani, Farida Al; Gerber, Susan I.; Hall, Aron J.; Al Muhairi, Salama

2017-01-01

Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population. PMID:28902913

The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.

PubMed

Radonovich, Lewis J; Bessesen, Mary T; Cummings, Derek A; Eagan, Aaron; Gaydos, Charlotte; Gibert, Cynthia; Gorse, Geoffrey J; Nyquist, Ann-Christine; Reich, Nicholas G; Rodrigues-Barradas, Maria; Savor-Price, Connie; Shaffer, Ronald E; Simberkoff, Michael S; Perl, Trish M

2016-06-02

Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).

Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune System

USDA-ARS?s Scientific Manuscript database

This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis and control. Worldwide PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic...

Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

PubMed

Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

2018-06-01

The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Distribution of bovine alpha-herpesviruses and expression of toll-like receptors in the respiratory system of experimentally infected calves.

PubMed

Marin, M S; Quintana, S; Leunda, M R; Odeón, A C; Pérez, S E

2016-04-01

This study provides an initial analysis of the toll-like receptors (TLRs) that might be implicated in alpha-herpesvirus infection of the bovine respiratory system. A significant variation in the expression of TLR3 and TLRs 7-9 during bovine herpesvirus type 1 (BoHV-1) and 5 (BoHV-5) acute infections and particularly an up-regulation during viral reactivation in respiratory tissues has been demonstrated. Furthermore, viral distribution in the respiratory tract of BoHV-1- and BoHV-5-infected calves at different stages of the infectious cycle was analysed. The wide distribution of BoHV DNA in the respiratory tract during acute infection was restricted during latent infection and the subsequent reactivation of BoHV-1 and BoHV-5. Overall, the findings presented here contribute to the knowledge on the replication and dissemination of bovine alpha-herpesviruses. Furthermore, some of the immune factors triggered in the host that determine the different outcomes of infection by two closely related pathogens of cattle have been elucidated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4

PubMed Central

Coviello, Silvina; Wimmenauer, Vera; Polack, Fernando P; Irusta, Pablo M

2014-01-01

Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens. PMID:25483455

Identification of Information Types and Sources by the Public for Promoting Awareness of Middle East Respiratory Syndrome Coronavirus in Saudi Arabia

ERIC Educational Resources Information Center

Hoda, Jradi

2016-01-01

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of serious consequences caused by MERS Coronavirus (MERS-CoV). Saudi communities still lack awareness of available protective measures to prevent the transmission of the virus. It is necessary to explore the current information-seeking strategies and preferences for…

Strengthening the diagnostic capacity to detect Bio Safety Level 3 organisms in unusual respiratory viral outbreaks.

PubMed

van Asten, Liselotte; van der Lubben, Mariken; van den Wijngaard, Cees; van Pelt, Wilfrid; Verheij, Robert; Jacobi, Andre; Overduin, Pieter; Meijer, Adam; Luijt, Dirk; Claas, Eric; Hermans, Mirjam; Melchers, Willem; Rossen, John; Schuurman, Rob; Wolffs, Petra; Boucher, Charles; Bouchier, Charles; Schirm, Jurjen; Kroes, Louis; Leenders, Sander; Galama, Joep; Peeters, Marcel; van Loon, Anton; Stobberingh, Ellen; Schutten, Martin; Koopmans, Marion

2009-07-01

Experience with a highly pathogenic avian influenza outbreak in the Netherlands (2003) illustrated that the diagnostic demand for respiratory viruses at different biosafety levels (including BSL3), can increase unexpectedly and dramatically. We describe the measures taken since, aimed at strengthening national laboratory surge capacity and improving preparedness for dealing with diagnostic demand during outbreaks of (emerging) respiratory virus infections, including pandemic influenza virus. Academic and peripheral medical-microbiological laboratories collaborated to determine minimal laboratory requirements for the identification of viruses in the early stages of a pandemic or a large outbreak of avian influenza virus. Next, an enhanced collaborative national network of outbreak assistance laboratories (OAL) was set up. An inventory was made of the maximum diagnostic throughput that this network can deliver in a period of intensified demand. For an estimate of the potential magnitude of this surge demand, historical counts were calculated from hospital- and physician-based registries of patients presenting with respiratory symptoms. Number of respiratory physician-visits ranged from 140,000 to 615,000 per month and hospitalizations ranged from 3000 to 11,500 per month. The established OAL-network provides rapid diagnostic response with agreed quality requirements and a maximum throughput capacity of 1275 samples/day (38,000 per month), assuming other routine diagnostic work needs to be maintained. Thus surge demand for diagnostics for hospitalized cases (if not distinguishable from other respiratory illness) could be handled by the OAL network. Assessing etiology of community acquired acute respiratory infection however, may rapidly exceed the capacity of the network. Therefore algorithms are needed for triaging for laboratory diagnostics; currently this is not addressed in pandemic preparedness plans.

Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples.

PubMed

Arvia, Rosaria; Corcioli, Fabiana; Ciccone, Nunziata; Della Malva, Nunzia; Azzi, Alberta

2015-12-01

Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 10(3) copies/ml to 10(4) copies/ml. For parainfluenza virus 2 only it was 10(5) copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be

Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

PubMed

Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

2015-10-01

In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Infection prevention and control measures for acute respiratory infections in healthcare settings: an update.

PubMed

Seto, W H; Conly, J M; Pessoa-Silva, C L; Malik, M; Eremin, S

2013-01-01

Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as "opportunistic" airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting highrisk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.

Environmental Attributes to Respiratory Diseases of Small Ruminants

PubMed Central

Rahal, Anu; Ahmad, Abul Hasan; Prakash, Atul; Mandil, Rajesh; Kumar, Aruna T.

2014-01-01

Respiratory diseases are the major disease crisis in small ruminants. A number of pathogenic microorganisms have been implicated in the development of respiratory disease but the importance of environmental factors in the initiation and progress of disease can never be overemphasized. They irritate the respiratory tree producing stress in the microenvironment causing a decline in the immune status of the small ruminants and thereby assisting bacterial, viral, and parasitic infections to break down the tissue defense barriers. Environmental pollutants cause acute or chronic reactions as they deposit on the alveolar surface which are characterized by inflammation or fibrosis and the formation of transitory or persistent tissue manifestation. Some of the effects of exposures may be immediate, whereas others may not be evident for many decades. Although the disease development can be portrayed as three sets of two-way communications (pathogen-environment, host-environment, and host-pathogen), the interactions are highly variable. Moreover, the environmental scenario is never static; new compounds are introduced daily making a precise evaluation of the disease burden almost impossible. The present review presents a detailed overview of these interactions and the ultimate effect on the respiratory health of sheep and goat. PMID:24782941

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness.

PubMed

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-12-30

Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. 6 major hospitals in 2 districts of Beijing, China. Cluster randomised controlled trial. 245 index cases with ILI. Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. ACTRN12613000852752; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial

PubMed Central

Sung, Anthony D.; Sung, Julia A. M.; Thomas, Samantha; Hyslop, Terry; Gasparetto, Cristina; Long, Gwynn; Rizzieri, David; Sullivan, Keith M.; Corbet, Kelly; Broadwater, Gloria; Chao, Nelson J.; Horwitz, Mitchell E.

2016-01-01

Background. Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. Methods. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010–2014) compared with the premask period (2003–2009). Results. RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19–0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001). Conclusions. Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT. PMID:27481873

Association between breast-feeding and severity of acute viral respiratory tract infection.

PubMed

Vereen, Shanda; Gebretsadik, Tebeb; Hartert, Tina V; Minton, Patricia; Woodward, Kimberly; Liu, Zhouwen; Carroll, Kecia N

2014-09-01

In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was associated with decreased relative odds of a lower versus upper respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval: 0.42-0.99). There was not a significant association between breast-feeding and bronchiolitis severity score or length of hospital stay.

Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997-2010.

PubMed

B'Krong, Nguyen Thi Thuy Chinh; Minh, Ngo Ngoc Quang; Qui, Phan Tu; Chau, Tran Thi Hong; Nghia, Ho Dang Trung; Do, Lien Anh Ha; Nhung, Nguyen Ngoc; Van Vinh Chau, Nguyen; Thwaites, Guy; Van Tan, Le; van Doorn, H Rogier; Thanh, Tran Tan

2018-04-12

Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. Samples from patients with CNS infection (51 children - 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children - 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response.

Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus.

PubMed

Shephard, Adrian; Zybeshari, Stela

2015-11-01

Most respiratory tract infections are self-limiting and caused by viruses, and do not warrant antibiotic treatment. Despite this, patients with respiratory tract infections often receive antibiotics, fuelling the rise of antibiotic resistance. Therefore, there is a need to encourage patients to try alternative non-antibiotic therapies, which ideally treat the symptoms and the cause. Lozenges containing amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA lozenges) as well as lozenges containing hexylresorcinol have been shown to provide effective symptomatic relief for sore throat. In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. Both viruses were incubated with AMC/DCBA lozenge, placebo lozenge or the active ingredients (AMC/DCBA) as free substances, and parainfluenza virus type 3 was incubated with hexylresorcinol lozenge, placebo lozenge or hexylresorcinol as a free substance. Virucidal effects were observed with the active lozenges and the active ingredients as free substances against both parainfluenza virus type 3 and cytomegalovirus. Mean reductions in viral titre were significantly greater compared with placebo lozenge and peak effects were observed for the shortest incubation time, 1min. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. Use of such over-the-counter treatments for self-limiting respiratory tract infections may satisfy patients' desire for an anti-infective medication and reduce the demand for antibiotics. Copyright © 2015 Elsevier B.V. All rights reserved.

A Cross-sectional Surveillance Study of the Frequency and Etiology of Acute Respiratory Illness Among Pregnant Women.

PubMed

Hause, Anne M; Avadhanula, Vasanthi; Maccato, Maurizio L; Pinell, Phillip M; Bond, Nanette; Santarcangelo, Patricia; Ferlic-Stark, Laura; Munoz, Flor M; Piedra, Pedro A

2018-05-05

Other than influenza, little is known about the consequences of viral acute respiratory illness (ARI) on pregnant women and fetuses. Our objectives were to determine the frequency of ARI due to respiratory viruses and the associated clinical outcomes during pregnancy. Pregnant women in their second or third trimester were enrolled if they reported having symptoms of ARI or were healthy within the preceding 2 weeks. Nasopharyngeal secretions were evaluated for respiratory viruses by molecular diagnostic assays. Clinical outcomes were evaluated at enrollment and via a follow-up telephone-based questionnaire 2 weeks later. There were 155 pregnant participants, with 81 ARI cases and 91 healthy controls. Acute lower respiratory tract illness (ALRTI) was identified in 29 cases (36%). Human rhinovirus (HRV), respiratory syncytial virus (RSV), and influenza virus accounted for 75% of virus-positive cases of ALRTI. Cases with ALRTI often reported a longer duration of illness, history of allergies, symptoms of wheezing, shortness of breath, or chest pain, and use of prescription medication. Two cases with ALRTI reported decreased fetal movement; a third case with ALRTI was hospitalized. In over one third of ARI cases, participants had symptoms consistent with ALRTI. Infection with HRV, RSV, or influenza virus was commonly detected in patients with ALRTI. Viral ALRTI during pregnancy appears to be common and is associated with significant morbidity.

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

PubMed Central

Kay, Linda; Parker, Lisa C.; Sabroe, Ian; Sleeman, Matthew A.; Briend, Emmanuel; Finch, Donna K.

2013-01-01

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses. PMID:23723976

Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

PubMed

Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

2015-09-01

This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome. © 2015 Wiley Periodicals, Inc.

Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

PubMed

Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

2010-05-14

The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

Viral infections in acute graft-versus-host disease: a review of diagnostic and therapeutic approaches.

PubMed

Tong, Lana X; Worswick, Scott D

2015-04-01

While immunosuppressive therapy for acute graft-versus-host disease (aGVHD) advances, viral reactivation has been found to be an increasingly common complication in these patients. Dermatologists may often be consulted on inpatient services for evaluation. We investigated the literature for the role of viral infections in aGVHD and review the current evidence regarding management. Articles in the public domain regarding aGVHD, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses, parvovirus B19, and respiratory viruses were included. Dermatologic findings vary between different viral antigens, and some infections may be a marker for the development of aGVHD or worsen prognosis. The heterogeneous cohorts of the studies reviewed often preclude direct comparison between results. The relationship between viral reactivation and aGVHD may be bidirectional and is worthy of further exploration. Additional studies are needed to determine appropriate prophylaxis and treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology.

PubMed

Pyle, Chloe J; Uwadiae, Faith I; Swieboda, David P; Harker, James A

2017-09-01

Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27.

Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology

PubMed Central

Swieboda, David P.

2017-01-01

Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27. PMID:28953978

Viruses in bronchiectasis: a pilot study to explore the presence of community acquired respiratory viruses in stable patients and during acute exacerbations.

PubMed

Mitchell, Alicia B; Mourad, Bassel; Buddle, Lachlan; Peters, Matthew J; Oliver, Brian G G; Morgan, Lucy C

2018-05-22

Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently.

Risk factors for severe bronchiolitis caused by respiratory virus infections among Mexican children in an emergency department

PubMed Central

Robledo-Aceves, Mireya; Moreno-Peregrina, María de Jesús; Velarde-Rivera, Fernando; Ascencio-Esparza, Elba; Preciado-Figueroa, Francisco M.; Caniza, Miguela A.; Escobedo-Melendez, Griselda

2018-01-01

Abstract Severe bronchiolitis is the most common reason for hospitalization among children younger than 2 years. This study analyzed the prevalence of community-acquired respiratory virus infection and the risk factors for hospitalization of Mexican children with severe bronchiolitis treated in an Emergency department. This retrospective study included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched controls. The study period was September 2012 to January 2015. We determined the viral etiology and coinfections with multiple viruses and compared the risk factors detected in children with severe viral bronchiolitis with those in the control group. A total of 153 respiratory viruses in these 134 patients, single or mixed infections, were identified: respiratory syncytial virus (RSV) type A or B was the most frequently detected (23.6% and 17.6%, respectively), followed by rhinovirus (RV; 16.3%) and parainfluenza virus (PIV) type 3 (12.4%). Coinfections of 2 respiratory viruses were found in 14.2% of cases; all cases had either RSV type A or B with another virus, the most common being parainfluenza virus or rhinovirus. Exposure to cigarette smoking was independently associated with hospitalization for severe bronchiolitis (OR, 3.5; 95% CI, 1.99–6.18; P = .0001), and having completed the vaccination schedule for their age was a protective factor against adverse outcome (OR, 0.55; 95% CI, 0.35–0.87; P = .010). RSV is a common infection among young children with severe bronchiolitis; thus, developing a vaccine against RSV is essential. Campaigns to reinforce the importance of avoiding childhood exposure to cigarette smoke are also needed. PMID:29489664

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Antibiotic and Diagnostic Discordance Between ED Physicians and Hospitalists for Pediatric Respiratory Illness.

PubMed

Coon, Eric R; Maloney, Christopher G; Shen, Mark W

2015-03-01

Imperfect diagnostic tools make it difficult to know the extent to which a bacterial process is contributing to respiratory illness, complicating the decision to prescribe antibiotics. We sought to quantify diagnostic and antibiotic prescribing disagreements between emergency department (ED) and pediatric hospitalist physicians for children admitted with respiratory illness. Manual chart review was used to identify testing, diagnostic, and antibiotic prescribing decisions for consecutive children admitted for respiratory illness in a winter (starting February 20, 2012) and a summer (starting August 20, 2012) season to a tertiary, freestanding children's hospital. Respiratory illness diagnoses were grouped into 3 categories: bacterial, viral, and asthma. A total of 181 children admitted for respiratory illness were studied. Diagnostic discordance was significant for all 3 types of respiratory illness but greatest for bacterial (P<.001). Antibiotic prescribing discordance was significant (P<.001), with pediatric hospitalists changing therapy for 93% of patients prescribed antibiotics in the ED, including stopping antibiotics altogether for 62% of patients. Significant diagnostic and antibiotic discordance between ED and pediatric hospitalist physicians exists for children admitted to the hospital for respiratory illness. Copyright © 2015 by the American Academy of Pediatrics.

Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

PubMed Central

Song, Huai-Dong; Tu, Chang-Chun; Zhang, Guo-Wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-Qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua; Chen, Sai-Juan; Luo, Hui-Ming; Zhou, Duan-Hua; Liu, Yu-Fei; He, Jian-Feng; Qin, Peng-Zhe; Li, Ling-Hui; Ren, Yu-Qi; Liang, Wen-Jia; Yu, Ye-Dong; Anderson, Larry; Wang, Ming; Xu, Rui-Heng; Wu, Xin-Wei; Zheng, Huan-Ying; Chen, Jin-Ding; Liang, Guodong; Gao, Yang; Liao, Ming; Fang, Ling; Jiang, Li-Yun; Li, Hui; Chen, Fang; Di, Biao; He, Li-Juan; Lin, Jin-Yan; Tong, Suxiang; Kong, Xiangang; Du, Lin; Hao, Pei; Tang, Hua; Bernini, Andrea; Yu, Xiao-Jing; Spiga, Ottavia; Guo, Zong-Ming; Pan, Hai-Yan; He, Wei-Zhong; Manuguerra, Jean-Claude; Fontanet, Arnaud; Danchin, Antoine; Niccolai, Neri; Li, Yi-Xue; Wu, Chung-I; Zhao, Guo-Ping

2005-01-01

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003. PMID:15695582

Effects of Human Metapneumovirus and Respiratory Syncytial Virus Antigen Insertion in Two 3′ Proximal Genome Positions of Bovine/Human Parainfluenza Virus Type 3 on Virus Replication and Immunogenicity

PubMed Central

Tang, Roderick S.; Schickli, Jeanne H.; MacPhail, Mia; Fernandes, Fiona; Bicha, Leenas; Spaete, Joshua; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Spaete, Richard; Haller, Aurelia A.

2003-01-01

A live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory syncytial virus (RSV). RSV and hMPV are both paramyxoviruses that cause respiratory disease in young children, the elderly, and immunocompromised individuals. RSV has been known for decades to cause acute lower respiratory tract infections in young children, which often result in hospitalization, while hMPV has only been recently identified as a novel human respiratory pathogen. In this study, the ability of bovine/human PIV3 to express three different foreign transmembrane surface glycoproteins and to induce a protective immune response was evaluated. The RNA-dependent RNA polymerase of paramyxoviruses binds to a single site at the 3′ end of the viral RNA genome to initiate transcription of viral genes. The genome position of the viral gene determines its level of gene expression. The promoter-proximal gene is transcribed with the highest frequency, and each downstream gene is transcribed less often due to attenuation of transcription at each gene junction. This feature of paramyxoviruses was exploited using the PIV3 vector by inserting the foreign viral genes at the 3′ terminus, at position 1 or 2, of the viral RNA genome. These locations were expected to yield high levels of foreign viral protein expression stimulating a protective immune response. The immunogenicity and protection results obtained with a hamster model showed that bovine/human PIV3 can be employed to generate bivalent PIV3/RSV or PIV3/hMPV vaccine candidates that will be further evaluated for safety and efficacy in primates. PMID:14512532

The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin.

PubMed

Kim, Young-In; Pareek, Rajat; Murphy, Ryan; Harrison, Lisa; Farrell, Eric; Cook, Robert; DeVincenzo, John

2017-11-01

Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract. We evaluated a novel RSV fusion inhibitor, MDT-637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans. MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations. The IC 50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50 s. We also measured MDT-637 IC 50 s in 3 lab strains and 4 clinical strains. The IC 50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC 50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial.

PubMed

Sung, Anthony D; Sung, Julia A M; Thomas, Samantha; Hyslop, Terry; Gasparetto, Cristina; Long, Gwynn; Rizzieri, David; Sullivan, Keith M; Corbet, Kelly; Broadwater, Gloria; Chao, Nelson J; Horwitz, Mitchell E

2016-10-15

Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010-2014) compared with the premask period (2003-2009). RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19-0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001). Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

PubMed Central

Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

2014-01-01

Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. PMID:25014738

Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam.

PubMed

Alroy, Karen A; Do, Trang Thuy; Tran, Phu Dac; Dang, Tan Quang; Vu, Long Ngoc; Le, Nga Thi Hang; Dang, Anh Duc; Ngu, Nghia Duy; Ngo, Tu Huy; Hoang, Phuong Vu Mai; Phan, Lan Trong; Nguyen, Thuong Vu; Nguyen, Long Thanh; Nguyen, Thinh Viet; Vien, Mai Quang; Le, Huy Xuan; Dao, Anh The; Nguyen, Trieu Bao; Pham, Duoc Tho; Nguyen, Van Thi Tuyet; Pham, Thanh Ngoc; Phan, Binh Hai; Whitaker, Brett; Do, Thuy Thi Thu; Dao, Phuong Anh; Balajee, S Arunmozhi; Mounts, Anthony W

2018-05-13

In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity

PubMed Central

Chenon, Mélanie; Camborde, Laurent; Cheminant, Soizic; Jupin, Isabelle

2012-01-01

Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity. PMID:22117220

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non-asthmatic Patients with Bacterial, Viral or Mixed Lung Infection.

PubMed

Giuffrida, M J; Valero, N; Mosquera, J; Duran, A; Arocha, F; Chacín, B; Espina, L M; Gotera, J; Bermudez, J; Mavarez, A; Alvarez-Mon, M

2017-04-01

This study was aimed to determine the profiles of serum cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status. © 2017 The Foundation for the Scandinavian Journal of Immunology.

Frequency of respiratory viruses among patients admitted to 26 Intensive Care Units in seven consecutive winter-spring seasons (2009-2016) in Northern Italy.

PubMed

Piralla, Antonio; Mariani, Bianca; Rovida, Francesca; Baldanti, Fausto

2017-07-01

The role of respiratory viruses in the etiology of community-acquired pneumonia (CAP) is still debated. The advent of molecular assays has improved the identification of viruses in patients with CAP and according to published studies, viruses account for 11-55% of adult CAP cases. In the present study, the frequency of respiratory viruses was evaluated in respiratory samples collected from 414 patients with CAP admitted to 26 ICUs in the Lombardy Region (10 million inhabitants) during seven winter-spring seasons (2009-2016). In 226 (54.6%) patients one or more respiratory viruses were identified, while 188 (45.4%) patients were negative. A single virus infection was observed in 214/226 (94.7%) patients; while, in 12/226 (5.3%) at least two respiratory viruses were detected. Influenza A was the most common virus in 140/226 patients (61.9%) followed by rhinoviruses (33/226, 14.6%), respiratory syncytial virus (13/226, 5.8%), influenza B virus (9/226, 4.0%), human coronaviruses (9/226, 4.0%), cytomegalovirus (9/226, 4.0%) and human metapneumovirus (1/226, 0.4%). Viral infections are present in a consistent proportion of patients admitted to the ICU for CAP. Influenza A and rhinovirus accounted for three-quarters of all CAP in ICU patients. The use of lower respiratory instead of upper respiratory samples might be useful in the diagnosis of viral CAP. Copyright © 2017 Elsevier B.V. All rights reserved.

Murine Coronavirus Ubiquitin-Like Domain Is Important for Papain-Like Protease Stability and Viral Pathogenesis

PubMed Central

Mielech, Anna M.; Deng, Xufang; Chen, Yafang; Kindler, Eveline; Wheeler, Dorthea L.; Mesecar, Andrew D.; Thiel, Volker; Perlman, Stanley

2015-01-01

ABSTRACT Ubiquitin-like domains (Ubls) now are recognized as common elements adjacent to viral and cellular proteases; however, their function is unclear. Structural studies of the papain-like protease (PLP) domains of coronaviruses (CoVs) revealed an adjacent Ubl domain in severe acute respiratory syndrome CoV, Middle East respiratory syndrome CoV, and the murine CoV, mouse hepatitis virus (MHV). Here, we tested the effect of altering the Ubl adjacent to PLP2 of MHV on enzyme activity, viral replication, and pathogenesis. Using deletion and substitution approaches, we identified sites within the Ubl domain, residues 785 to 787 of nonstructural protein 3, which negatively affect protease activity, and valine residues 785 and 787, which negatively affect deubiquitinating activity. Using reverse genetics, we engineered Ubl mutant viruses and found that AM2 (V787S) and AM3 (V785S) viruses replicate efficiently at 37°C but generate smaller plaques than wild-type (WT) virus, and AM2 is defective for replication at higher temperatures. To evaluate the effect of the mutation on protease activity, we purified WT and Ubl mutant PLP2 and found that the proteases exhibit similar specific activities at 25°C. However, the thermal stability of the Ubl mutant PLP2 was significantly reduced at 30°C, thereby reducing the total enzymatic activity. To determine if the destabilizing mutation affects viral pathogenesis, we infected C57BL/6 mice with WT or AM2 virus and found that the mutant virus is highly attenuated, yet it replicates sufficiently to elicit protective immunity. These studies revealed that modulating the Ubl domain adjacent to the PLP reduces protease stability and viral pathogenesis, revealing a novel approach to coronavirus attenuation. IMPORTANCE Introducing mutations into a protein or virus can have either direct or indirect effects on function. We asked if changes in the Ubl domain, a conserved domain adjacent to the coronavirus papain-like protease, altered

Diarrheal and Respiratory Illness Surveillance During US-RP Balikatan 2014.

PubMed

Velasco, John M; Valderamat, Maria T; Nogrado, Kathyleen; Wongstitwilairoong, Tippa; Swierczewski, Brett; Bodhidatta, Ladaporn; Lertsethtakarn, Paphavee; Klungthong, Chonticha; Fernandez, Stefan; Mason, Carl; Yoon, In-Kyu; Macareo, Louis

2015-06-01

Diarrheal and respiratory illness surveillance was conducted during the 2014 Republic of the Philippines-U.S. Exercise Balikatan in the Philippines. Seven stool and three respiratory specimens that met the inclusion criteria were collected. Diarrhea stool specimens were tested with commercial enzyme-linked immunosorbent assay kits and real-time polymerase chain reaction (PCR) for 12 viral, bacterial, and protozoan pathogens. Campylobacter, enterotoxigenic Escherichia coli (ETEC), and enteropathogenic Escherichia coli (EPEC) were detected in four of seven (57%), two of seven (29%), and four of seven (57%) specimens, respectively. There were co-infections of EPEC and ETEC in two cases and EPEC and Campylobacter spp. in one case. Respiratory samples were tested using RT-PCR. One of three samples was positive for influenza B. Laboratory-based surveillance is important in determining causative agents for illnesses experienced by military personnel during deployment. Development of vaccines for enteric diseases should be expedited to mitigate their impact on operational readiness.

Sore throat in primary care project: a clinical score to diagnose viral sore throat.

PubMed

Mistik, Selcuk; Gokahmetoglu, Selma; Balci, Elcin; Onuk, Fahri A

2015-06-01

Viral agents cause the majority of sore throats. However, there is not currently a score to diagnose viral sore throat. The aims of this study were (i) to find the rate of bacterial and viral causes, (ii) to show the seasonal variations and (iii) to form a new scoring system to diagnose viral sore throat. A throat culture for group A beta haemolytic streptococci (GABHS) and a nasopharyngeal swab to detect 16 respiratory viruses were obtained from each patient. Over a period of 52 weeks, a total of 624 throat cultures and polymerase chain reaction analyses were performed. Logistic regression analysis was performed to find the clinical score. Viral infection was found in 277 patients (44.3%), and GABHS infection was found in 116 patients (18.5%). An infectious cause was found in 356 patients (57.1%). Rhinovirus was the most commonly detected infectious agent overall (highest in November, 34.5%), and the highest GABHS rate was in November (32.7%). Analysis of data provided a scoring system, called the Mistik Score, to diagnose viral sore throat. The predictive model for positive viral analysis included the following variables: absence of headache, stuffy nose, sneezing, temperature of ≥37.5°C on physical examination, and the absence of tonsillar exudate and/or swelling. The probability of a positive viral analysis for a score of 5 was 82.1%. The Mistik Score may be useful to diagnose viral sore throat. We suggest its use either alone or in combination with the Modified Centor Score. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

E-mail-based symptomatic surveillance combined with self-collection of nasal swabs: a new tool for acute respiratory infection epidemiology.

PubMed

Akmatov, Manas K; Krebs, Stephan; Preusse, Matthias; Gatzemeier, Anja; Frischmann, Ursula; Schughart, Klaus; Pessler, Frank

2011-11-01

We examined the feasibility of combining communication by e-mail and self-collection of nasal swabs for the prospective detection of acute respiratory infections in a non-medical setting. The study was conducted among a convenience sample of employees (n=53) at a research institution (December 2009-April 2010). Real-time data on the occurrence of acute respiratory symptoms and a nasal self-swab were collected prospectively, with automated weekly e-mails as a reminder mechanism. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect respiratory viral pathogens in the swabs. Fifty-one out of 53 participants completed the study. The study design was well accepted. Thirty (∼57%) participants reported at least one episode of acute respiratory infection and returned the nasal swab during the study period (eight participants reported two episodes). The majority had no difficulties taking the self-swab and preferred this to swabbing by study personnel. Most participants obtained and returned the swabs within the recommended time. Viral respiratory pathogens were detected in 19 of 38 swabs (50%), with coronaviruses 229E/NL63 and OC43 and rhinoviruses A and B constituting 17 positive swabs (89%). Combining e-mail-based symptomatic surveillance with nasal self-swabbing promises to be a powerful tool for the real-time identification of incident cases of acute respiratory infections and the associated pathogens in population-based studies. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Duox2-induced innate immune responses in the respiratory epithelium and intranasal delivery of Duox2 DNA using polymer that mediates immunization.

PubMed

Jeon, Yung Jin; Kim, Hyun Jik

2018-05-01

Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism. In respiratory epithelium, Duox2-derived ROS is critical for recognition of virus through families retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) at the early stage of antiviral innate immune responses. Various secreted interferons (IFNs) play essential roles for antiviral host defense by downstream cell signaling, and transcription of IFN-stimulated genes is started to suppress viral replication. Type I and type III IFNs are verified more responsible for influenza A virus (IAV) infection in respiratory epithelium and Duox2 is required to regulate IFN-related immune responses. Transient overexpression of Duox2 using cationic polymer polyethylenimine (PEI) induces secretion of type I and type III IFNs and significantly attenuated IAV replication in respiratory epithelium. Here, we discuss Duox2-mediated antiviral innate immune responses and the role of Duox2 as a mucosal vaccine to resist respiratory viral infection.

Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels

PubMed Central

Adney, Danielle R.; van Doremalen, Neeltje; Brown, Vienna R.; Bushmaker, Trenton; Scott, Dana; de Wit, Emmie; Munster, Vincent J.

2014-01-01

In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission. PMID:25418529

Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission.

PubMed

Oma, Veslemøy Sunniva; Tråvén, Madeleine; Alenius, Stefan; Myrmel, Mette; Stokstad, Maria

2016-06-13

Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. A live animal experiment was conducted, with direct contact between animal groups for 24 h as challenge procedure. Four naïve calves were commingled with a group of six naturally infected calves and sequentially euthanized. Two naïve sentinel calves were commingled with the experimentally exposed group three weeks after exposure. Nasal swabs, feces, blood and tissue samples were analyzed for viral RNA by RT-qPCR, and virus isolation was performed on nasal swabs. Serum was analyzed for BCoV antibodies. The calves showed mild general signs, and the most prominent signs were from the respiratory system. The overall clinical score corresponded well with the shedding of viral RNA the first three weeks after challenge. General depression and cough were the signs that correlated best with shedding of BCoV RNA, while peak respiratory rate and peak rectal temperature appeared more than a week later than the peak shedding. Nasal shedding preceded fecal shedding, and the calves had detectable amounts of viral RNA intermittently in feces through day 35 and in nasal secretions through day 28, however virus isolation was unsuccessful from day six and day 18 from the two calves investigated. Viral RNA was not detected in blood, but was found in lymphatic tissue through day 42 after challenge. Although the calves were shedding BCoV RNA 21 days after infection the sentinel animals were not infected

Bovine viral diarrhea viruses (BVDV) and their cousins the HoBi-like viruses: Multi symptom, multi host, multi tasking pathogens

USDA-ARS?s Scientific Manuscript database

The term bovine viral diarrhea (BVD) has come to refer to a diverse collection of clinical presentations that include respiratory, enteric and reproductive symptoms accompanied by immunosuppression. While the majority of cases are subclinical in nature two forms exist, mucosal disease and hemorrhag...

Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread

PubMed Central

McCarty, Thomas; Martin, Scott E.; Le Nouën, Cyril; Buehler, Eugen; Chen, Yu-Chi; Smelkinson, Margery; Ganesan, Sundar; Fischer, Elizabeth R.; Brock, Linda G.; Liang, Bo; Munir, Shirin; Collins, Peter L.; Buchholz, Ursula J.

2016-01-01

Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells. Consistent with reduced spread, there was a 10-fold reduction in the release of infectious progeny virions in ARP2-depleted cells at 72 hr post-infection. In addition, we found that RSV infection induced filopodia formation and increased cell motility in A549 cells and that this phenotype was ARP2 dependent. Filopodia appeared to shuttle RSV to nearby uninfected cells, facilitating virus spread. Expression of the RSV F protein alone from a plasmid or heterologous viral vector in A549 cells induced filopodia, indicating a new role for the RSV F protein, driving filopodia induction and virus spread. Thus, this study identified roles for ARP2 and filopodia in RSV-induced cell motility, RSV production, and RSV cell-to-cell spread. PMID:27926942

Ferret models of viral pathogenesis.

PubMed

Enkirch, T; von Messling, V

2015-05-01

Emerging and well-known viral diseases remain one the most important global public health threats. A better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. Here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. We will describe the anatomic and physiologic characteristics that contribute to the natural susceptibility of ferrets to these viruses, and provide an overview of the approaches available to analyze their immune responses. Recent insights gained using this model will be highlighted, including the development of new prophylactic and therapeutic approaches. To provide decision criteria for the use of this animal model, its strengths and limitations will be discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

EXPOSURE TO URBAN AIR PARTICULATES ALTERS THE MACROPHAGE- MEDIATED INFLAMMATORY RESPONSE TO RESPIRATORY VIRAL INFECTION

EPA Science Inventory

Epidemiology studies associate increased pulmonary morbidity with episodes of high particulate air pollution (size range 0.1-10 microm diameter, PM10). Pneumonia, often viral in origin, is increased following episodes of high PM10 pollution. Therefore, this study was undertaken t...

Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

Identification of a novel nidovirus in an outbreak of fatal respiratory disease in ball pythons (Python regius).

PubMed

Uccellini, Lorenzo; Ossiboff, Robert J; de Matos, Ricardo E C; Morrisey, James K; Petrosov, Alexandra; Navarrete-Macias, Isamara; Jain, Komal; Hicks, Allison L; Buckles, Elizabeth L; Tokarz, Rafal; McAloose, Denise; Lipkin, Walter Ian

2014-08-08

Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents are only infrequently identified. Pneumonia, tracheitis and esophagitis were reported in a collection of ball pythons (Python regius). Eight of 12 snakes had evidence of bacterial pneumonia. High-throughput sequencing of total extracted nucleic acids from lung, esophagus and spleen revealed a novel nidovirus. PCR indicated the presence of viral RNA in lung, trachea, esophagus, liver, and spleen. In situ hybridization confirmed the presence of intracellular, intracytoplasmic viral nucleic acids in the lungs of infected snakes. Phylogenetic analysis based on a 1,136 amino acid segment of the polyprotein suggests that this virus may represent a new species in the subfamily Torovirinae. This report of a novel nidovirus in ball pythons may provide insight into the pathogenesis of respiratory disease in this species and enhances our knowledge of the diversity of nidoviruses.

Viral Infections

MedlinePlus

... to fight it off. For most viral infections, treatments can only help with symptoms while you wait ... for viral infections. There are antiviral medicines to treat some viral infections. Vaccines can help prevent you ...

Actinobacillus pleuropneumoniae culture supernatant antiviral effect against porcine reproductive and respiratory syndrome virus occurs prior to the viral genome replication and transcription through actin depolymerization.

PubMed

Hernandez Reyes, Yenney; Provost, Chantale; Traesel, Carolina Kist; Jacques, Mario; Gagnon, Carl A

2018-02-01

Recently, the strong antiviral activity of an Actinobacillus pleuropneumoniae (App) culture supernatant against porcine reproductive and respiratory syndrome virus (PRRSV) was discovered. Following this finding, the objective of the present study was to understand how the App culture supernatant inhibits PRRSV replication in its natural targeted host cells, i.e. porcine alveolar macrophages (PAMs). Several assays were conducted with App culture supernatant-treated PRRSV-infected cell lines, such as PAM, St-Jude porcine lung and MARC-145 cells. RT-qPCR assays were used to determine the expression levels of type I and II IFN mRNAs, viral genomic (gRNA) and sub-genomic RNAs (sgRNAs). Proteomic, Western blot and immunofluorescence assays were conducted to determine the involvement of actin filaments in the App culture supernatant antiviral effect.Results/Key findings. Type I and II IFN mRNA expressions were not upregulated by the App culture supernatant. Time courses of gRNA and sgRNA expression levels demonstrated that the App culture supernatant inhibits PRRSV infection before the first viral transcription cycle. Western blot experiments confirmed an increase in the expression of cofilin (actin cytoskeleton dynamics regulator) and immunofluorescence also demonstrated a significant decrease of actin filaments in App culture supernatant-treated PRRSV-infected PAM cells. App culture supernatant antiviral activity was also demonstrated against other PRRSV strains of genotypes I and II. App culture supernatant antiviral effect against PRRSV takes place early during PRRSV infection. Results suggest that App culture supernatant antiviral effect may take place via the activation of cofilin, which induces actin depolymerization and subsequently, probably affects PRRSV endocytosis. Other experiments are needed to fully validate this latest hypothesis.

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

PubMed

Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

2018-01-09

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Nuclear targeting of viral and non-viral DNA.

PubMed

Chowdhury, E H

2009-07-01

The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins.

Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil.

PubMed

Pilger, Diogo André; Cantarelli, Vlademir Vicente; Amantea, Sérgio Luis; Leistner-Segal, Sandra

2011-02-01

The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV) and human bocavirus (hBoV), in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA) metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV), influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.

Influenza and other respiratory viruses in three Central American countries.

PubMed

Laguna-Torres, Victor A; Sánchez-Largaespada, José F; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E; Halsey, Eric S; Kochel, Tadeusz J

2011-03-01

Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. To analyze viral etiologic agents associated with influenza-like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Genetic analysis of influenza isolates identified A (H3N2), A (H1N1), and B viruses. It also showed that the mutation H274Y conferring resistance to oseltamivir was first detected in Honduran influenza A/H1N1 strains at the beginning of 2008. These data demonstrate that a diverse range of respiratory

Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

PubMed Central

Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

2016-01-01

In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

The innate immune response to RSV: Advances in our understanding of critical viral and host factors.

PubMed

Sun, Yan; López, Carolina B

2017-01-11

Respiratory syncytial virus (RSV) causes mild to severe respiratory illness in humans and is a major cause of hospitalizations of infants and the elderly. Both the innate and the adaptive immune responses contribute to the control of RSV infection, but despite successful viral clearance, protective immunity against RSV re-infection is usually suboptimal and infections recur. Poor understanding of the mechanisms limiting the induction of long-lasting immunity has delayed the development of an effective vaccine. The innate immune response plays a critical role in driving the development of adaptive immunity and is thus a crucial determinant of the infection outcome. Advances in recent years have improved our understanding of cellular and viral factors that influence the onset and quality of the innate immune response to RSV. These advances include the identification of a complex system of cellular sensors that mediate RSV detection and stimulate transcriptome changes that lead to virus control and the discovery that cell stress and apoptosis participate in the control of RSV infection. In addition, it was recently demonstrated that defective viral genomes (DVGs) generated during RSV replication are the primary inducers of the innate immune response. Newly discovered host pathways involved in the innate response to RSV, together with the potential generation of DVG-derived oligonucleotides, present various novel opportunities for the design of vaccine adjuvants able to induce a protective response against RSV and similar viruses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

PubMed

Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

2016-04-01

Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line

PubMed Central

Sarmiento, Rosa E; Tirado, Rocio G; Valverde, Laura E; Gómez-Garcia, Beatriz

2007-01-01

Background The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV) antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2) were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs) and intracellular viral proteins were detected by indirect immunoflourescence. Results Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death. Conclusion The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell. PMID:17608950

Evaluation of Alere i RSV for Rapid Detection of Respiratory Syncytial Virus in Children Hospitalized with Acute Respiratory Tract Infection.

PubMed

Peters, Rebecca Marie; Schnee, Sarah Valerie; Tabatabai, Julia; Schnitzler, Paul; Pfeil, Johannes

2017-04-01

Alere i RSV is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. In this study, we evaluated the Alere i RSV assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. Alere i RSV assay results were compared to those for Altona RealStar RSV real-time reverse transcription-PCR (RT-PCR). We found that the overall sensitivity and specificity of the Alere i RSV test was 100% (95% confidence intervals [CI], 93% to 100%) and 97% (95% CI, 89% to 100%), respectively. Positive samples were identified within 5 to 7 min from sample collection. Overall, the Alere i RSV test performed well compared to the RT-PCR assay and has the potential to facilitate the detection of RSV in point-of-care settings. Copyright © 2017 Peters et al.

Quantitative analysis of Porcine Reproductive and Respiratory Syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant viral disease facing the global swine industry. Viremia profiles of PRRS virus challenged pigs reflect the severity and progression of the infection within the host and provide crucial information for subsequen...

Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia.

PubMed

Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

2016-01-01

Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases.

Respiratory herpesvirus infection in two Indian Ringneck parakeets.

PubMed

Lazic, Tatjana; Ackermann, Mark R; Drahos, Jo M; Stasko, Judith; Haynes, Joseph S

2008-03-01

A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.

Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5

PubMed Central

Yang, Yang; Zengel, James; Sun, Minghao; Sleeman, Katrina; Timani, Khalid Amine; Aligo, Jason; Rota, Paul

2015-01-01

ABSTRACT Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the N-terminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses. IMPORTANCE We identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the

Detection of pathogens in Boidae and Pythonidae with and without respiratory disease.

PubMed

Schmidt, V; Marschang, R E; Abbas, M D; Ball, I; Szabo, I; Helmuth, R; Plenz, B; Spergser, J; Pees, M

2013-03-02

Respiratory diseases in boid snakes are common in captivity, but little information is available on their aetiology. This study was carried out to determine the occurrence of lung associated pathogens in boid snakes with and without respiratory signs and/or pneumonia. In total, 80 boid snakes of the families Boidae (n = 30) and Pythonidae (n = 50) from 48 private and zoo collections were included in this survey. Husbandry conditions were evaluated using a detailed questionnaire. All snakes were examined clinically and grouped into snakes with or without respiratory signs. Tracheal wash samples from all snakes were examined bacteriologically as well as virologically. All snakes were euthanased, and a complete pathological examination was performed. Respiratory signs and pneumonia were detected more often in pythons than in boas. An acute catarrhal pneumonia was diagnosed more often in snakes without respiratory signs than in snakes with respiratory signs, which revealed fibrinous and fibrous pneumonia. Poor husbandry conditions are an important trigger for the development of respiratory signs and pneumonia. Different bacterial pathogens were isolated in almost all snakes with pneumonia, with Salmonella species being the most common. Ferlavirus (formerly known as ophidian paramyxovirus)-RNA was detected only in pythons. Inclusion body disease was rarely seen in pythons but often in boas. Adenovirus and Mycoplasma were other pathogens that were diagnosed in single snakes with pneumonia. In living boid snakes with respiratory signs, tracheal wash samples were found to be a useful diagnostic tool for the detection of viral and bacterial pathogens.

Lactobacillus johnsonii Supplementation Attenuates Respiratory Viral Infection via Metabolic Reprogramming and Immune Cell Modulation

PubMed Central

Fonseca, Wendy; Lucey, Kaitlyn; Jang, Sihyug; Fujimura, Kei E.; Rasky, Andrew; Ting, Hung-An; Petersen, Julia; Johnson, Christine C.; Boushey, Homer A.; Zoratti, Edward; Ownby, Dennis R.; Levine, Albert M.; Bobbit, Kevin R.

2017-01-01

Summary Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii-supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii-supplementation reduced airway Th2 cytokines, dendritic cell function, increased T-regulatory cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone-marrow derived dendritic cells (BMDC) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice, or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice, or with wild-type derived BMDCs pre-treated with plasma from L. johnsonii-supplemented mice, reduced airway pathologic responses to infection in recipient animals. Thus, L. johnsonii-supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function. PMID:28295020

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

PubMed

Fonseca, W; Lucey, K; Jang, S; Fujimura, K E; Rasky, A; Ting, H-A; Petersen, J; Johnson, C C; Boushey, H A; Zoratti, E; Ownby, D R; Levine, A M; Bobbit, K R; Lynch, S V; Lukacs, N W

2017-11-01

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Porcine reproductive and respiratory syndrome type 1 viruses induce hypoplasia of erythroid cells and myeloid cell hyperplasia in the bone marrow of experimentally infected piglets independently of the viral load and virulence.

PubMed

Amarilla, Shyrley Paola; Gómez-Laguna, Jaime; Carrasco, Librado; Rodríguez-Gómez, Irene M; Caridad Y Ocerín, José M; Graham, Simon P; Frossard, Jean-Pierre; Steinbach, Falko; Salguero, Francisco J

2017-03-01

Porcine reproductive and respiratory syndrome viruses (PRRSV) present a wide phenotypic and genetic diversity. Experimental infections have demonstrated viral replication, including highly pathogenic strains (HP-PRRSV), in primary lymphoid organs such as the thymus. However, studies of the bone marrow are scarce but necessary to help elucidate the immunobiology of PRRSV strains of differing virulence. In this study, whereas viral RNA was detected within the bone marrow of animals experimentally infected with both low virulent Lelystad (LV) and 215-06 PRRSV-1 strains and with the highly virulent SU1-bel strain, PRRSV positive cells were only occasionally detected in one SU1-bel infected animal. PRRSV RNA levels were associated to circulating virus with the highest levels detected in LV-infected pigs. At 3 dpi, a decrease in the proportion of haematopoietic tissue and number of erythroid cells in all infected groups was associated with an increase in TUNEL or cleaved caspase 3 labelling and higher counts of myeloid cells compared to control. The expression of IL-1α and IL-6 was elevated at the beginning of the infection in all infected animals. The expression of TNF-α was increased at the end of the study in all infected groups with respect to control. Different PRRSV-1 strains induced, presummably by indirect mechanisms and independently of viral load and strain virulence, moderate and sustained hypoplasia of erythroid cells and myeloid cell hyperplasia at early stages of infection. These changes were paralleled by a peak in the local expression of IL-1α, IL-6 and TNF-α in all infected groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Randomized, Placebo-Controlled Clinical Trial of Oral Azithromycin Prophylaxis Against Respiratory Infections in a High-Risk, Young Adult Population

DTIC Science & Technology

2001-10-01

infection, (2) pneumonia, and (3) cellulitis or folliculitis acute respiratory infection viral and bacterial etiology studies, requiring systemic...acute respiratory infection 6.5 12.9 0.50 (0.28-0.92) Pneumonia 3.2 5.2 0.62 (0.25-1.52) Cellulitis or folliculitis 10.6 13.7 0.78 (0.47-1.28) Attrition...477 (93%) of 511 trainees were enrolled. The 2 study 57 were treated with antibiotics for cellulitis or folliculitis . All groups had very similar

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

PubMed

Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System.

PubMed

Lunney, Joan K; Fang, Ying; Ladinig, Andrea; Chen, Nanhua; Li, Yanhua; Rowland, Bob; Renukaradhya, Gourapura J

2016-01-01

This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis, and control. Worldwide, PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic mechanisms, and host immunity, with a special focus on immune factors that modulate PRRSV infections during the acute and chronic/persistent disease phases. We address genetic control of host resistance and probe effects of PRRSV infection on reproductive traits. A major goal is to identify cellular/viral targets and pathways for designing more effective vaccines and therapeutics. Based on progress in viral reverse genetics, host transcriptomics and genomics, and vaccinology and adjuvant technologies, we have identified new areas for PRRS control and prevention. Finally, we highlight the gaps in our knowledge base and the need for advanced molecular and immune tools to stimulate PRRS research and field applications.

Viral meningitis.

PubMed

Chadwick, David R

2005-01-01

Viruses probably account for most cases of acute meningitis. Viral meningitis is often assumed to be a largely benign disease. For the commonest pathogens causing meningitis, enteroviruses, this is usually the case; however, for many of the other pathogens causing viral meningitis, and for common pathogens in the immunocompromised or infants, viral meningitis is frequently associated with substantial neurological complications and a significant mortality. Diagnostic methods for rapid and accurate identification of pathogens have improved over recent years, permitting more precise and earlier diagnoses. There have been fewer developments in therapies for viral meningitis, and there remain no effective therapies for most pathogens, emphasising the importance of prevention and early diagnosis. This review focuses on the presentation, diagnosis and management of viral meningitis and also covers the prevention of meningitis for pathogens where effective vaccines are available.

Clinical and laboratory description of a series of cases of acute viral myositis.

PubMed

Cardin, Silvana Paula; Martin, Joelma Gonçalves; Saad-Magalhães, Claudia

2015-01-01

Describe the clinical and laboratory profile, follow-up, and outcome of a series of cases of acute viral myositis. A retrospective analysis of suspected cases under observation in the emergency department was performed, including outpatient follow-up with the recording of respiratory infection and musculoskeletal symptoms, measurement of muscle enzymes, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), transaminases (AST and ALT), blood count, C-reactive protein, and erythrocyte sedimentation rate in the acute phase and during follow-up until normalization. Between 2000 and 2009, 42 suspected cases were identified and 35 (27 boys) were included. The median age was 7 years and the diagnosis was reported in 89% in the first emergency visit. The observed respiratory symptoms were cough (31%), rhinorrhea (23%), and fever (63%), with a mean duration of 4.3 days. Musculoskeletal symptoms were localized pain in the calves (80%), limited ambulation (57%), gait abnormality (40%), and muscle weakness in the lower limbs (71%), with a mean duration of 3.6 days. There was significant increase in CPK enzymes (5507±9180U/L), LDH (827±598U/L), and AST (199±245U/L), with a tendency to leukopenia (4590±1420) leukocytes/mm(3). The complete recovery of laboratory parameters was observed in 30 days (median), and laboratory and clinical recurrence was documented in one case after 10 months. Typical symptoms with increased muscle enzymes after diagnosis of influenza and self-limited course of the disease were the clues to the diagnosis. The increase in muscle enzymes indicate transient myotropic activity related to seasonal influenza, which should be considered, regardless of the viral identification, possibly associated with influenza virus or other respiratory viruses. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Persistent bovine viral diarrhea virus (BVDV) infection in cattle herds

PubMed Central

Khodakaram-Tafti, A.; Farjanikish, GH.

2017-01-01

Bovine viral diarrhea virus (BVDV) is a significant pathogen associated with gastrointestinal, respiratory, and reproductive diseases of cattle worldwide. It causes continuous economic losses to the cattle industry primarily due to decreased reproductive performance. The ability of virus to cross the placenta during early pregnancy can result in the birth of persistently infected (PI) calves. Persistently infected animals are generally much more efficient transmitters of BVDV than transiently or acutely infected animals because they are capable of shedding large quantities of virus throughout their lives and are considered the primary reservoirs for BVDV. Due to the nature of viral infections, there is no treatment to fully cure an animal of a viral infection. All control programs which are in use in many countries of the world, mainly depend upon the detection of PI animals, eliminating them and preventing their return into the herds. Detection of PI animals at early stage, particularly soon after birth is of significant benefit to implement BVDV control programs. Available diagnostic tests such as virus isolation (VI), immunohistochemistry (IHC), Antigen-Capture ELISA (ACE), and reverse transcriptase polymerase chain reaction (RT-PCR) are used for detection of PI cattle. Each method to detect BVDV has advantages, disadvantages, and applicability for different diagnostic situations. The reliability of diagnostic tests is optimized by choosing the appropriate sampling strategy on the basis of animal age. PMID:29163643

Nitric oxide metabolites as biomarkers for influenza-like acute respiratory infections presenting to the emergency room.

PubMed

Mian, Asad I; Laham, Federico R; Cruz, Andrea T; Garg, Harsha; Macias, Charles G; Caviness, A Chantal; Piedra, Pedro A

2012-01-01

Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic. Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR. Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002). Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner.

Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials.

PubMed

Hayden, Frederick G; Coats, Teresa; Kim, Kenneth; Hassman, Howard A; Blatter, Mark M; Zhang, Bing; Liu, Siyu

2002-03-01

We evaluated the efficacy and tolerability of oral pleconaril, an anti-picornavirus agent, in treating acute viral respiratory illness (VRI) in two double-blind, placebo-controlled trials. Otherwise healthy subjects, 14 years of age or older, who presented within 36 h of VRI symptom onset, were randomized to pleconaril 400 mg or matching placebo in liquid (first trial) or tablet (second trial) formulations twice-daily (first trial only) or three-times daily for 7 days. The infected subjects from the corresponding active and placebo groups (three-times daily dosing regimens) were combined for analysis. Among the subset of subjects with proven picornaviral infection in both studies (42% of total enrolled), pleconaril 400 mg three-times daily (n = 323) reduced the time to alleviation of illness (no rhinorrhoea and other symptoms mild or absent for > or = 48 h) compared with placebo (n = 264) (median: 10.0 days for placebo and 8.5 days for pleconaril; P = 0.029). In addition, pleconaril reduced the time to a > or = 50% reduction from baseline in total symptom severity score (median: 4.5 days for placebo and 3.5 days for pleconaril; P = 0.038). Significant reductions in the number of tissues used for nose-blowing (20% reduction) and in nights of disturbed sleep (16% reduction) were also observed. Pleconaril was generally well tolerated; the liquid formulation caused gastrointestinal disturbance in all groups (diarrhoea 10-14%, nausea 5-9%, abdominal discomfort 6-8%), and tablets were associated with a greater incidence of nausea (3% for placebo versus 7% for pleconaril, P = 0.003). Pleconaril 400 mg administered three-times daily reduced the duration and severity of picornaviral VRI in adolescents and adults.

Formation of a stable mimic of ambient particulate matter containing viable infectious respiratory syncytial virus and its dry-deposition directly onto cell cultures.

PubMed

Cruz-Sanchez, Teresita M; Haddrell, Allen E; Hackett, Tillie L; Singhera, Gurpreet K; Marchant, David; Lekivetz, Ryan; Meredith, Anna; Horne, Derrick; Knight, Darryl A; van Eeden, Stephen F; Bai, Tony R; Hegele, Richard G; Dorscheid, Delbert R; Agnes, George R

2013-01-15

Epidemiological associations of worse respiratory outcomes from combined exposure to ambient particulate matter (PM) and respiratory viral infection suggest possible interactions between PM and viruses. To characterize outcomes of such exposures, we developed an in vitro mimic of the in vivo event of exposure to PM contaminated with respiratory syncytial virus (RSV). Concentration of infectious RSV stocks and a particle levitation apparatus were the foundations of the methodology developed to generate specific numbers of PM mimics (PM(Mimics)) of known composition for dry, direct deposition onto airway epithelial cell cultures. Three types of PM(Mimics) were generated for this study: (i) carbon alone (P(C)), (ii) carbon and infectious RSV (P(C+RSV)), and (iii) aerosols consisting of RSV (A(RSV)). P(C+RSV) were stable in solution and harbored infectious RSV for up to 6 months. Unlike A(RSV) infection, P(C+RSV) infection was found to be dynamin dependent and to cause lysosomal rupture. Cells dosed with PM(Mimics) comprised of RSV (A(RSV)), carbon (P(C)), or RSV and carbon (P(C+RSV)) responded differentially as exemplified by the secretion patterns of IL-6 and IL-8. Upon infection, and prior to lung cell death due to viral infection, regression analysis of these two mediators in response to incubation with A(RSV), P(C), or P(C+RSV) yielded higher concentrations upon infection with the latter and at earlier time points than the other PM(Mimics). In conclusion, this experimental platform provides an approach to study the combined effects of PM-viral interactions and airway epithelial exposures in the pathogenesis of respiratory diseases involving inhalation of environmental agents.

Respiratory disease in ball pythons (Python regius) experimentally infected with ball python nidovirus.

PubMed

Hoon-Hanks, Laura L; Layton, Marylee L; Ossiboff, Robert J; Parker, John S L; Dubovi, Edward J; Stenglein, Mark D

2018-04-01

Circumstantial evidence has linked a new group of nidoviruses with respiratory disease in pythons, lizards, and cattle. We conducted experimental infections in ball pythons (Python regius) to test the hypothesis that ball python nidovirus (BPNV) infection results in respiratory disease. Three ball pythons were inoculated orally and intratracheally with cell culture isolated BPNV and two were sham inoculated. Antemortem choanal, oroesophageal, and cloacal swabs and postmortem tissues of infected snakes were positive for viral RNA, protein, and infectious virus by qRT-PCR, immunohistochemistry, western blot and virus isolation. Clinical signs included oral mucosal reddening, abundant mucus secretions, open-mouthed breathing, and anorexia. Histologic lesions included chronic-active mucinous rhinitis, stomatitis, tracheitis, esophagitis and proliferative interstitial pneumonia. Control snakes remained negative and free of clinical signs throughout the experiment. Our findings establish a causal relationship between nidovirus infection and respiratory disease in ball pythons and shed light on disease progression and transmission. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.

PubMed

Jia, Nan; Barclay, Wendy S; Roberts, Kim; Yen, Hui-Ling; Chan, Renee W Y; Lam, Alfred K Y; Air, Gillian; Peiris, J S Malik; Dell, Anne; Nicholls, John M; Haslam, Stuart M

2014-10-10

The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2-3- and α2-6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1-4)Galβ1-4GlcNAc) and sialylated N,N'-diacetyllactosamine (NeuAcα2-6GalNAcβ1-4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Infections in hemodialysis: a concise review - Part 1: bacteremia and respiratory infections

PubMed Central

Eleftheriadis, T; Liakopoulos, V; Leivaditis, K; Antoniadi, G; Stefanidis, I

2011-01-01

Hemodialysis (HD) patients are particularly predisposed to infections. It seems that the HD procedure per se as well as disturbances in both innate and adaptive immunity significantly contribute to this susceptibility. Infections are the major cause of morbidity and the second cause of death following cardiovascular events in HD patients. Episodes of bacteremia and pneumonia account for the majority of severe infections in this population. In addition to these bacterial infections another common problem in HD units is the blood transmitted viral infections, particularly infections caused by hepatitis B virus, hepatitis C virus and Human immunodeficiency virus. A number of safety concerns exist for limiting the spread of these viral infections among HD patients and the staff of the unit. The aim of the present review is to present in a concise albeit practical form the difficult aspect of infections in HD. For practical reasons the review is separated in two parts. The present first part covers bacteremia and respiratory infections, while the second part will cover blood transmitted viral infections. PMID:21607029

Rapid one-step construction of a Middle East Respiratory Syndrome (MERS-CoV) infectious clone system by homologous recombination.

PubMed

Nikiforuk, Aidan M; Leung, Anders; Cook, Bradley W M; Court, Deborah A; Kobasa, Darwyn; Theriault, Steven S

2016-10-01

Viral Infectious clone systems serve as robust platforms to study viral gene or replicative function by reverse genetics, formulate vaccines and adapt a wild type-virus to an animal host. Since the development of the first viral infectious clone system for the poliovirus, novel strategies of viral genome construction have allowed for the assembly of viral genomes across the identified viral families. However, the molecular profiles of some viruses make their genome more difficult to construct than others. Two factors that affect the difficulty of infectious clone construction are genome length and genome complexity. This work examines the available strategies for overcoming the obstacles of assembling the long and complex RNA genomes of coronaviruses and reports one-step construction of an infectious clone system for the Middle East Respiratory Syndrome coronavirus (MERS-CoV) by homologous recombination in S. cerevisiae. Future use of this methodology will shorten the time between emergence of a novel viral pathogen and construction of an infectious clone system. Completion of a viral infectious clone system facilitates further study of a virus's biology, improvement of diagnostic tests, vaccine production and the screening of antiviral compounds. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections

PubMed Central

2018-01-01

ABSTRACT Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability. PMID:29764948

Racial and Ethnic Differences in Antibiotic Use for Viral Illness in Emergency Departments.

PubMed

Goyal, Monika K; Johnson, Tiffani J; Chamberlain, James M; Casper, T Charles; Simmons, Timothy; Alessandrini, Evaline A; Bajaj, Lalit; Grundmeier, Robert W; Gerber, Jeffrey S; Lorch, Scott A; Alpern, Elizabeth R

2017-10-01

In the primary care setting, there are racial and ethnic differences in antibiotic prescribing for acute respiratory tract infections (ARTIs). Viral ARTIs are commonly diagnosed in the pediatric emergency department (PED), in which racial and ethnic differences in antibiotic prescribing have not been previously reported. We sought to investigate whether patient race and ethnicity was associated with differences in antibiotic prescribing for viral ARTIs in the PED. This is a retrospective cohort study of encounters at 7 PEDs in 2013, in which we used electronic health data from the Pediatric Emergency Care Applied Research Network Registry. Multivariable logistic regression was used to examine the association between patient race and ethnicity and antibiotics administered or prescribed among children discharged from the hospital with viral ARTI. Children with bacterial codiagnoses, chronic disease, or who were immunocompromised were excluded. Covariates included age, sex, insurance, triage level, provider type, emergency department type, and emergency department site. Of 39 445 PED encounters for viral ARTIs that met inclusion criteria, 2.6% (95% confidence interval [CI] 2.4%-2.8%) received antibiotics, including 4.3% of non-Hispanic (NH) white, 1.9% of NH black, 2.6% of Hispanic, and 2.9% of other NH children. In multivariable analyses, NH black (adjusted odds ratio [aOR] 0.44; CI 0.36-0.53), Hispanic (aOR 0.65; CI 0.53-0.81), and other NH (aOR 0.68; CI 0.52-0.87) children remained less likely to receive antibiotics for viral ARTIs. Compared with NH white children, NH black and Hispanic children were less likely to receive antibiotics for viral ARTIs in the PED. Future research should seek to understand why racial and ethnic differences in overprescribing exist, including parental expectations, provider perceptions of parental expectations, and implicit provider bias. Copyright © 2017 by the American Academy of Pediatrics.

[Upper respiratory tract infections and sports].

PubMed

Boffi El Amari, Emmanuelle

2010-08-11

Upper respiratory tract infections are frequent in athletes. Mainly of viral origin, they are treated symptomatically. Infectious mononucleosis is associated with an estimated 2% per hundred risk of splenic rupture, which occurs between day four and twenty one of the illness. Therefore return to play guidelines recommend avoiding, exercice during the first twenty one days. Physical exercise seems to influence the immune system, depending on the intensity and length of it. But the relationship between physical exercise and risk of infections remains controversial: some articles showing an increase in risk, whereas others suggesting a certain degree of protection, in athletes. The actual generally accepted working theory is the J-curve proposed by Nieman. This model remains to be formally proven.

Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

PubMed Central

Stenglein, Mark D.; Jacobson, Elliott R.; Wozniak, Edward J.; Wellehan, James F. X.; Kincaid, Anne; Gordon, Marcus; Porter, Brian F.; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S.

2014-01-01

ABSTRACT A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. PMID:25205093

Comparative analytical evaluation of the respiratory TaqMan Array Card with real-time PCR and commercial multi-pathogen assays.

PubMed

Harvey, John J; Chester, Stephanie; Burke, Stephen A; Ansbro, Marisela; Aden, Tricia; Gose, Remedios; Sciulli, Rebecca; Bai, Jing; DesJardin, Lucy; Benfer, Jeffrey L; Hall, Joshua; Smole, Sandra; Doan, Kimberly; Popowich, Michael D; St George, Kirsten; Quinlan, Tammy; Halse, Tanya A; Li, Zhen; Pérez-Osorio, Ailyn C; Glover, William A; Russell, Denny; Reisdorf, Erik; Whyte, Thomas; Whitaker, Brett; Hatcher, Cynthia; Srinivasan, Velusamy; Tatti, Kathleen; Tondella, Maria Lucia; Wang, Xin; Winchell, Jonas M; Mayer, Leonard W; Jernigan, Daniel; Mawle, Alison C

2016-02-01

In this study, a multicenter evaluation of the Life Technologies TaqMan(®) Array Card (TAC) with 21 custom viral and bacterial respiratory assays was performed on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The goal of the study was to demonstrate the analytical performance of this platform when compared to identical individual pathogen specific laboratory developed tests (LDTs) designed at the Centers for Disease Control and Prevention (CDC), equivalent LDTs provided by state public health laboratories, or to three different commercial multi-respiratory panels. CDC and Association of Public Health Laboratories (APHL) LDTs had similar analytical sensitivities for viral pathogens, while several of the bacterial pathogen APHL LDTs demonstrated sensitivities one log higher than the corresponding CDC LDT. When compared to CDC LDTs, TAC assays were generally one to two logs less sensitive depending on the site performing the analysis. Finally, TAC assays were generally more sensitive than their counterparts in three different commercial multi-respiratory panels. TAC technology allows users to spot customized assays and design TAC layout, simplify assay setup, conserve specimen, dramatically reduce contamination potential, and as demonstrated in this study, analyze multiple samples in parallel with good reproducibility between instruments and operators. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of semiconductor fluorescent nanocrystals as optical probes for rapid early viral detection

NASA Astrophysics Data System (ADS)

Bentzen, Elizabeth L.; House, Frances; Tomlinson, Ian D.; Rosenthal, Sandra J.; Crowe, James E.; Wright, David D.

2005-04-01

Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Non-specific binding is a frequently encountered problem with fluorescent labeling in biological assays. In these studies various cell lines were examined for non-specific binding to quantum dots. Evidence suggests that non-specific binding is related to cell type and, may be significantly reduced by functionalizing quantum dots with polyethyleneglycol ligands (PEG). In addition quantum dots were used to detect and monitor the progession of the viral glycoproteins ,F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

Pharyngitis - viral

MedlinePlus

... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...

Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

PubMed Central

Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

2015-01-01

Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

PubMed Central

Tilton, Susan C.; Menachery, Vineet D.; Gralinski, Lisa E.; Schäfer, Alexandra; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Chang, Jean; Luna, Maria L.; Long, Casey E.; Shukla, Anil K.; Bankhead, Armand R.; Burkett, Susan E.; Zornetzer, Gregory; Tseng, Chien-Te Kent; Metz, Thomas O.; Pickles, Raymond; McWeeney, Shannon; Smith, Richard D.; Katze, Michael G.; Waters, Katrina M.; Baric, Ralph S.

2013-01-01

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo. PMID:23365422

Recombinant porcine reproductive and respiratory syndrome virus expressing luciferase genes provide a new indication of viral propagation in both permissive and target cells.

PubMed

Gao, Fei; Qu, Zehui; Li, Liwei; Yu, Lingxue; Jiang, Yifeng; Zhou, Yanjun; Yang, Shen; Zheng, Hao; Huang, Qinfeng; Tong, Wu; Tong, Guangzhi

2016-08-01

Porcine reproductive and respiratory syndrome virus (PRRSV) has a condensed single-stranded positive-sense RNA genome that contains several overlapping regions. The transcription regulatory sequence (TRS) is the important cis-acting element participating in PRRSV discontinuous transcription process. Based on reverse genetic system of type 2 highly pathogenic PRRSV cell-passage attenuated strain pHuN4-F112, firefly luciferase or Renilla luciferase genes were inserted between ORF1b and ORF2. An extra TRS6 was embedded behind the foreign luciferase genes. pA-Fluc and pA-Rluc were constructed and successfully rescued in MARC-145 cells. The phenotypical characteristics of the progeny virus were indistinguishable from those of vHuN4-F112 and were genetically stable for at least 25 cell passages. Mutant virus-infected cells were lysed at different time points to assess luciferase activities and measure foreign gene expression levels. The results showed identical variations in the luciferase activities of the recombinants in MARC-145 cells, indicating that they were suitable for monitoring viral propagation in PRRSV-permissive cell cultures. They were also used to infect pulmonary alveolar macrophages, which yielded similar variations in luciferase activities. Therefore, vA-Fluc and vA-Rluc present powerful new tools to monitor PRRSV propagation in both passaged and target cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses.

PubMed

Ederveen, Thomas H A; Ferwerda, Gerben; Ahout, Inge M; Vissers, Marloes; de Groot, Ronald; Boekhorst, Jos; Timmerman, Harro M; Huynen, Martijn A; van Hijum, Sacha A F T; de Jonge, Marien I

2018-01-11

While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA. Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels. The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.

Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

PubMed

Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuka; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

2018-05-31

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Complete genome sequence of highly virulent Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) variants that recently emerged in the United States

USDA-ARS?s Scientific Manuscript database

A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe dise...

Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro

PubMed Central

Webb, Stacy R.; Smith, Stacy E.; Fried, Michael G.

2018-01-01

ABSTRACT Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens—Ebola virus, influenza virus, SARS CoV, and rabies virus—self-associate. This observation across various viral

Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent

PubMed Central

Li, Linlin; Deng, Xutao; Mee, Edward T.; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D.; Delwart, Eric

2014-01-01

Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries on the efficiency of viral detection and virus genome coverage were compared. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. PMID:25497414

Management of Respiratory Infections with Use of Procalcitonin: Moving toward More Personalized Antibiotic Treatment Decisions.

PubMed

Wirz, Yannick; Branche, Angela; Wolff, Michel; Welte, Tobias; Nobre, Vandack; Reinhart, Konrad; Falsey, Ann R; Damas, Pierre; Beishuizen, Albertus; Deliberato, Rodrigo O; Shehabi, Yahya; Jensen, Jens-Ulrik S; Mueller, Beat; Schuetz, Philipp

2017-12-08

Due to overlap of clinical findings and low sensitivity of bacterial diagnostic tests, differentiation between bacterial and viral respiratory tract infections remains challenging, ultimately leading to antibiotic overuse in this population of patients. Addition of procalcitonin, a blood biomarker expressed by epithelial cells in response to bacterial infections, to the clinical assessment leads to a reduction in inappropriate antibiotic initiation. Procalcitonin also provides prognostic information about the resolution of illness, and significant decreases over time are a strong signal for the discontinuation of antibiotics. Current evidence from randomized trials indicates that procalcitonin-guided antibiotic stewardship results in a reduction in antibiotic use and antibiotic side effects, which importantly translates into improved survival of patients with respiratory infections. Inclusion of procalcitonin into antibiotic stewardship algorithms thus improves the diagnostic and therapeutic management of patients presenting with respiratory illnesses and holds great promise to mitigate the global bacterial resistance crisis.

The Role of Human Milk Immunomodulators in Protecting Against Viral Bronchiolitis and Development of Chronic Wheezing Illness.

PubMed

Dixon, Dani-Louise

2015-07-07

Infants who are breastfed are at an immunological advantage when compared with formula fed infants, evidenced by decreased incidence of infections and diminished propensity for long term conditions, including chronic wheeze and/or asthma. Exclusive breastfeeding reduces the duration of hospital admission, risk of respiratory failure and requirement for supplemental oxygen in infants hospitalised with bronchiolitis suggesting a potentially protective mechanism. This review examines the evidence and potential pathways for protection by immunomodulatory factors in human milk against the most common viral cause of bronchiolitis, respiratory syncytial virus (RSV), and subsequent recurrent wheeze in infants. Further investigations into the interplay between respiratory virus infections such as RSV and how they affect, and are affected by, human milk immunomodulators is necessary if we are to gain a true understanding of how breastfeeding protects many infants but not all against infections, and how this relates to long-term protection against conditions such as chronic wheezing illness or asthma.

INFLUENZA-INDUCED UP-REGULATION OF TLR3 IN RESPIRATORY EPITHELIAL CELLS MAY OCCUR THROUGH A POSITIVE FEEDBACK LOOP INVOLVING TYPE I INTERFERON

EPA Science Inventory

Toll-like receptor 3 (TLR3) plays an important role in the host defense responses against viral infections, including Influenza virus infections. Based on our previous observations showing that Influenza infection of respiratory epithelial cells results in an up-regulation of Tol...

Porcine Reproductive and Respiratory Syndrome Virus Utilizes Nanotubes for Intercellular Spread

PubMed Central

Guo, Rui; Katz, Benjamin B.; Tomich, John M.; Gallagher, Tom

2016-01-01

ABSTRACT Intercellular nanotube connections have been identified as an alternative pathway for cellular spreading of certain viruses. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nanotubes were observed connecting two distant cells with contiguous membranes, with the core infectious viral machinery (viral RNA, certain replicases, and certain structural proteins) present in/on the intercellular nanotubes. Live-cell movies tracked the intercellular transport of a recombinant PRRSV that expressed green fluorescent protein (GFP)-tagged nsp2. In MARC-145 cells expressing PRRSV receptors, GFP-nsp2 moved from one cell to another through nanotubes in the presence of virus-neutralizing antibodies. Intercellular transport of viral proteins did not require the PRRSV receptor as it was observed in receptor-negative HEK-293T cells after transfection with an infectious clone of GFP-PRRSV. In addition, GFP-nsp2 was detected in HEK-293T cells cocultured with recombinant PRRSV-infected MARC-145 cells. The intercellular nanotubes contained filamentous actin (F-actin) with myosin-associated motor proteins. The F-actin and myosin IIA were identified as coprecipitates with PRRSV nsp1β, nsp2, nsp2TF, nsp4, nsp7-nsp8, GP5, and N proteins. Drugs inhibiting actin polymerization or myosin IIA activation prevented nanotube formation and viral clusters in virus-infected cells. These data lead us to propose that PRRSV utilizes the host cell cytoskeletal machinery inside nanotubes for efficient cell-to-cell spread. This form of virus transport represents an alternative pathway for virus spread, which is resistant to the host humoral immune response. IMPORTANCE Extracellular virus particles transmit infection between organisms, but within infected hosts intercellular infection can be spread by additional mechanisms. In this study, we describe an alternative pathway for intercellular transmission of PRRSV in which the virus uses nanotube connections to

Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.

PubMed

Weinberg, Adriana; Mussi-Pinhata, Marisa M; Yu, Qilu; Cohen, Rachel A; Almeida, Volia C; Amaral, Fabiana R; Freimanis, Laura; Harris, Donald Robert; Smith, Christiana; Siberry, George

2018-06-01

To identify factors that predispose human immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization, and death in the first 6-24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. Nested case-control study of 107 LRTI+ infants enrolled in the International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries (LILAC) studies with and 140 LRTI- in the first 6 months, matched by date and place of birth. Infants and mothers had plasma antibodies measured against respiratory syncytial virus (RSV), parainfluenza (PIV) 1, 2, 3, influenza, and pneumococcus 1, 5, 6B, and 14. Compared with LRTI-, mothers of LRTI+ HEUs had lower years of education, lower CD4 + cells, and higher HIV plasma viral load at delivery, but similar use of antiretrovirals and cotrimoxazole and other sociodemographic characteristics. LRTI+ and LRTI- HEUs had similar demographic and hematological characteristics and antibody concentrations against respiratory pathogens at birth. At 6 months, the rates of seroconversions to respiratory pathogens and antibody responses to tetanus vaccine were also similar. However, antibody concentrations to RSV were significantly higher in LRTI+ compared with LRTI- HEUs and marginally higher to PIV1. Maternal factors associated with advanced HIV disease, but unrelated to the use of antiretrovirals, cotrimoxazole, or the level of maternal antibodies against respiratory pathogens, contribute to the increased risk of LRTI in HEUs. In HEUs, antiretroviral and cotrimoxazole use, exposure to respiratory pathogens and humoral immune responses were not associated with the incidence of LRTI.

Parainfluenza virus as a cause of acute respiratory infection in hospitalized children.

PubMed

Pecchini, Rogério; Berezin, Eitan Naaman; Souza, Maria Cândida; Vaz-de-Lima, Lourdes de Andrade; Sato, Neuza; Salgado, Maristela; Ueda, Mirthes; Passos, Saulo Duarte; Rangel, Raphael; Catebelota, Ana

2015-01-01

Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group. Copyright © 2015. Published by Elsevier Editora Ltda.

Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

PubMed Central

Alshrari, Ahmed S.; Badroon, Nassrin A.; Hassan, Ahmed M.; Alsubhi, Tagreed L.; Ejeeli, Saleh

2017-01-01

We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control. PMID:28348590

Budesonide and Formoterol Reduce Early Innate Anti-Viral Immune Responses In Vitro

PubMed Central

Davies, Janet M.; Carroll, Melanie L.; Li, Hongzhuo; Poh, Alisa M.; Kirkegard, Darren; Towers, Michelle; Upham, John W.

2011-01-01

Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10−6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2′, 5′ oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance

A novel sampling method to detect airborne influenza and other respiratory viruses in mechanically ventilated patients: a feasibility study.

PubMed

Mitchell, Alicia B; Tang, Benjamin; Shojaei, Maryam; Barnes, Lachlan S; Nalos, Marek; Oliver, Brian G; McLean, Anthony S

2018-04-17

Respiratory viruses circulate constantly in the ambient air. The risk of opportunistic infection from these viruses can be increased in mechanically ventilated patients. The present study evaluates the feasibility of detecting airborne respiratory viruses in mechanically ventilated patients using a novel sample collection method involving ventilator filters. We collected inspiratory and expiratory filters from the ventilator circuits of mechanically ventilated patients in an intensive care unit over a 14-month period. To evaluate whether we could detect respiratory viruses collected in these filters, we performed a reverse transcription polymerase chain reaction on the extracted filter membrane with primers specific for rhinovirus, respiratory syncytial virus, influenza virus A and B, parainfluenza virus (type 1, 2 and 3) and human metapneumovirus. For each patient, we also performed a full virology screen (virus particles, antibody titres and virus-induced biomarkers) on respiratory samples (nasopharyngeal swab, tracheal aspirate or bronchoalveolar fluid) and blood samples. Respiratory viruses were detected in the ventilator filters of nearly half the patients in the study cohort (n = 33/70). The most common virus detected was influenza A virus (n = 29). There were more viruses detected in the inspiratory filters (n = 18) than in the expiratory filters (n = 15). A third of the patients with a positive virus detection in the ventilator filters had a hospital laboratory confirmed viral infection. In the remaining cases, the detected viruses were different from viruses already identified in the same patient, suggesting that these additional viruses come from the ambient air or from cross-contamination (staff or visitors). In patients in whom new viruses were detected in the ventilator filters, there was no evidence of clinical signs of an active viral infection. Additionally, the levels of virus-induced biomarker in these patients were not

A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region

PubMed Central

Gongora, Victor; Hartley, Dane; Oura, Christopher

2018-01-01

Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories. PMID:29373488

A multiplexed reverse transcriptase PCR assay for identification of viral respiratory pathogens at point-of-care

DOE Office of Scientific and Technical Information (OSTI.GOV)

Letant, S E; .Ortiz, J I; Tammero, L

2007-04-11

We have developed a nucleic acid-based assay that is rapid, sensitive, specific, and can be used for the simultaneous detection of 5 common human respiratory pathogens including influenza A, influenza B, parainfluenza type 1 and 3, respiratory syncytial virus, and adenovirus group B, C, and E. Typically, diagnosis on an un-extracted clinical sample can be provided in less than 3 hours, including sample collection, preparation, and processing, as well as data analysis. Such a multiplexed panel would enable rapid broad-spectrum pathogen testing on nasal swabs, and therefore allow implementation of infection control measures, and timely administration of antiviral therapies. Thismore » article presents a summary of the assay performance in terms of sensitivity and specificity. Limits of detection are provided for each targeted respiratory pathogen, and result comparisons are performed on clinical samples, our goal being to compare the sensitivity and specificity of the multiplexed assay to the combination of immunofluorescence and shell vial culture currently implemented at the UCDMC hospital. Overall, the use of the multiplexed RT-PCR assay reduced the rate of false negatives by 4% and reduced the rate of false positives by up to 10%. The assay correctly identified 99.3% of the clinical negatives, 97% of adenovirus, 95% of RSV, 92% of influenza B, and 77% of influenza A without any extraction performed on the clinical samples. The data also showed that extraction will be needed for parainfluenza virus, which was only identified correctly 24% of the time on un-extracted samples.« less

Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010-2012).

PubMed

Delangue, Julie; Roca Sanchez, Yelin; Piorkowski, Géraldine; Bessaud, Maël; Baronti, Cécile; Thirion-Perrier, Laurence; Mafayle, Roxana Loayza; Ardaya, Cinthia Avila; Aguilera, Gabriela Añez; Guzman, Jimmy Revollo; Riera, Javier Lora; de Lamballerie, Xavier

2014-02-24

Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0-4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

PubMed Central

Larios Mora, Alejandro; Detalle, Laurent; Van Geelen, Albert; Davis, Michael S.; Stohr, Thomas; Gallup, Jack M.; Ackermann, Mark R.

2015-01-01

Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and

Acute immunological responses to a combined viral-bacterial respiratory disease challenge in heifers administered transdermal flunixin meglumine

USDA-ARS?s Scientific Manuscript database

Time of flunixin meglumine transdermal (FTD; Finadyne Transdermal, Merck Animal Health, Summit, NJ) administration relative to a viral-bacterial challenge was evaluated in beef heifers. Thirty-two beef heifers (170 ± 21.1 kg BW) were randomly assigned to one of four treatments: 1) Control (CON), rec...

The spectrum of respiratory pathogens among returning Hajj pilgrims: myths and reality.

PubMed

Gautret, Phillipe; Benkouiten, Samir; Al-Tawfiq, Jaffar A; Memish, Ziad A

2016-06-01

Enhanced surveillance systems have been implemented recently in many countries in order to rapidly detect and investigate any possible cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection among travellers returning from the Middle East, including notably Hajj pilgrims. According to the available surveillance data, only a few sporadic travel-associated MERS-CoV cases have been reported outside the Arabian Peninsula so far, mainly in Europe, North Africa, and Asia. These have resulted in no cases, or limited numbers of secondary cases except in Korea. The vast majority of viral respiratory infections in pilgrims returning home have been due to seasonal influenza viruses, rhinoviruses, and other known coronaviruses distinct from the MERS coronavirus. Influenza vaccination should be a priority for all Hajj pilgrims, as recommended by experts. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

PubMed

Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

2017-03-18

Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

Novel Treatment with Neuroprotective and Antiviral Properties against a Neuroinvasive Human Respiratory Virus

PubMed Central

Brison, Elodie; Jacomy, Hélène

2014-01-01

ABSTRACT Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. IMPORTANCE PMID:24227863

An optimized methodology for whole genome sequencing of RNA respiratory viruses from nasopharyngeal aspirates.

PubMed

Goya, Stephanie; Valinotto, Laura E; Tittarelli, Estefania; Rojo, Gabriel L; Nabaes Jodar, Mercedes S; Greninger, Alexander L; Zaiat, Jonathan J; Marti, Marcelo A; Mistchenko, Alicia S; Viegas, Mariana

2018-01-01

Over the last decade, the number of viral genome sequences deposited in available databases has grown exponentially. However, sequencing methodology vary widely and many published works have relied on viral enrichment by viral culture or nucleic acid amplification with specific primers rather than through unbiased techniques such as metagenomics. The genome of RNA viruses is highly variable and these enrichment methodologies may be difficult to achieve or may bias the results. In order to obtain genomic sequences of human respiratory syncytial virus (HRSV) from positive nasopharyngeal aspirates diverse methodologies were evaluated and compared. A total of 29 nearly complete and complete viral genomes were obtained. The best performance was achieved with a DNase I treatment to the RNA directly extracted from the nasopharyngeal aspirate (NPA), sequence-independent single-primer amplification (SISPA) and library preparation performed with Nextera XT DNA Library Prep Kit with manual normalization. An average of 633,789 and 1,674,845 filtered reads per library were obtained with MiSeq and NextSeq 500 platforms, respectively. The higher output of NextSeq 500 was accompanied by the increasing of duplicated reads percentage generated during SISPA (from an average of 1.5% duplicated viral reads in MiSeq to an average of 74% in NextSeq 500). HRSV genome recovery was not affected by the presence or absence of duplicated reads but the computational demand during the analysis was increased. Considering that only samples with viral load ≥ E+06 copies/ml NPA were tested, no correlation between sample viral loads and number of total filtered reads was observed, nor with the mapped viral reads. The HRSV genomes showed a mean coverage of 98.46% with the best methodology. In addition, genomes of human metapneumovirus (HMPV), human rhinovirus (HRV) and human parainfluenza virus types 1-3 (HPIV1-3) were also obtained with the selected optimal methodology.

Birth Weight, Intrauterine Growth Retardation and Fetal Susceptibility to Porcine Reproductive and Respiratory Syndrome Virus

PubMed Central

Ladinig, Andrea; Foxcroft, George; Ashley, Carolyn; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

2014-01-01

The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection. PMID:25275491

Influence of parainfluenza-1 respiratory tract viral infection on endothelin receptor-effector systems in mouse and rat tracheal smooth muscle.

PubMed Central

Knott, P. G.; Henry, P. J.; McWilliam, A. S.; Rigby, P. J.; Fernandes, L. B.; Goldie, R. G.

1996-01-01

1. In this study we have compared the effects of parainfluenza-1 respiratory tract viral infection on the density and function of ETA and ETB receptors in rat and mouse tracheal airway smooth muscle. 2. The bronchoconstrictor effect of inhaled methacholine was significantly enhanced in virus-infected rats, at both 4 and 12 days post-inoculation. That is, the concentration of methacholine causing an increase in resistance of 100% (PC100 methacholine) was significantly lower in virus-infected animals at both 4 and 12 days post-inoculation (n = 6-8; P < 0.05). 3. Total specific binding of [125I]-endothelin-1 and the relative proportions of ETA and ETB binding sites for [125I]-endothelin-1 were assessed in tracheal airway smooth muscle in parainfluenza-1-infected rats and mice at days 2, 4 and 12 post-inoculation using the ligands BQ-123 (1 microM; ETA receptor-selective) and sarafotoxin S6c (100 nM; ETB receptor-selective). Total specific binding in mice was significantly reduced at day 2 post-inoculation (n = 5; P < 0.05) but not at days 4 and 12 post-inoculation (n = 5). In control mice, the proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day 4 and these were significantly altered by parainfluenza-1 infection such that, the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post-inoculation, the proportion of ETA and ETB binding sites in tracheal smooth muscle from mice infected with parainfluenza-1 was not significantly different from control. In rat tracheal airway smooth muscle, neither total specific binding nor the ETA and ETB binding site ratio (64%:36%) were significantly altered in virus-inoculated rats at days 2, 4 or 12 post-inoculation (n = 5). 4. Parainfluenza-1 infection in mice had no effect on the sensitivity or maximal contractile effect of endothelin-1 in tracheal smooth muscle at days 2, 4 or 12 post-inoculation (n = 4). In contrast, contraction in response to the ETB receptor-selective agonist

Mutational analysis reveals a noncontractile but interactive role of actin and profilin in viral RNA-dependent RNA synthesis.

PubMed

Harpen, Mary; Barik, Tiasha; Musiyenko, Alla; Barik, Sailen

2009-11-01

As obligatory parasites, viruses co-opt a variety of cellular functions for robust replication. The expression of the nonsegmented negative-strand RNA genome of respiratory syncytial virus (RSV), a significant pediatric pathogen, absolutely requires actin and is stimulated by the actin-regulatory protein profilin. As actin is a major contractile protein, it was important to determine whether the known functional domains of actin and profilin were important for their ability to activate RSV transcription. Analyses of recombinant mutants in a reconstituted RSV transcription system suggested that the divalent-cation-binding domain of actin is critically needed for binding to the RSV genome template and for the activation of viral RNA synthesis. In contrast, the nucleotide-binding domain and the N-terminal acidic domain were needed neither for template binding nor for transcription. Specific surface residues of actin, required for actin-actin contact during filamentation, were also nonessential for viral transcription. Unlike actin, profilin did not directly bind to the viral template but was recruited by actin. Mutation of the interactive residues of actin or profilin, resulting in the loss of actin-profilin binding, also abolished profilin's ability to stimulate viral transcription. Together, these results suggest that actin acts as a classical transcription factor for the virus by divalent-cation-dependent binding to the viral template and that profilin acts as a transcriptional cofactor, in part by associating with actin. This essential viral role of actin is independent of its contractile cellular role.

Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase.

PubMed

Adedeji, Adeyemi O; Singh, Kamalendra; Calcaterra, Nicholas E; DeDiego, Marta L; Enjuanes, Luis; Weiss, Susan; Sarafianos, Stefan G

2012-09-01

Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC(50)s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC(50)] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC(50)] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.

Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas.

PubMed

Camps, M; Vilella, A; Marcos, M A; Letang, E; Muñoz, J; Salvadó, E; González, A; Gascón, J; Jiménez de Anta, M T; Pumarola, T

2008-04-01

Fifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available.

Human coronavirus and severe acute respiratory infection in Southern Brazil.

PubMed

Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

2016-05-01

Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p < 0.001), and HCoV accounted for 6% of the SARI cases. Three patients infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

Canine viral infections.

PubMed

Willis, A M

2000-09-01

The ophthalmic effects of viral infection are varied. With the added possibility for pathologic effects of attenuated vaccine viruses, the diagnosis of viral diseases can be a challenge. In many cases, ocular manifestations can provide added support to a presumptive diagnosis of viral disease, thereby underscoring the benefit of thorough ophthalmic examination of any animal with nonspecific signs of illness.

Viral Epitranscriptomics

PubMed Central

Kennedy, Edward M.; Courtney, David G.; Tsai, Kevin

2017-01-01

ABSTRACT Although it has been known for over 40 years that eukaryotic mRNAs bear internal base modifications, it is only in the last 5 years that the importance of these modifications has begun to come into focus. The most common mRNA modification, the addition of a methyl group to the N6 position of adenosine (m6A), has been shown to affect splicing, translation, and stability, and m6A is also essential for embryonic development in organisms ranging from plants to mice. While all viral transcripts examined so far have been found to be extensively m6A modified, the role, if any, of m6A in regulating viral gene expression and replication was previously unknown. However, recent data generated using HIV-1 as a model system strongly suggest that sites of m6A addition not only are evolutionarily conserved but also enhance virus replication. It is therefore likely that the field of viral epitranscriptomics, which can be defined as the study of functionally relevant posttranscriptional modifications of viral RNA transcripts that do not change the nucleotide sequence of that RNA, is poised for a major expansion in scientific interest and may well fundamentally change our understanding of how viral replication is regulated. PMID:28250115

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

PubMed

Boikos, Constantina; Papenburg, Jesse; Martineau, Christine; Joseph, Lawrence; Scheifele, David; Chilvers, Mark; Lands, Larry C; De Serres, Gaston; Quach, Caroline

2017-06-03

The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. Influenza RNA was detected in 16% fewer participants (95% CrI: -7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: -16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: -2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: -0.37, 1.26). The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and -negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis

PubMed Central

Boikos, Constantina; Papenburg, Jesse; Martineau, Christine; Joseph, Lawrence; Scheifele, David; Chilvers, Mark; Lands, Larry C.; De Serres, Gaston; Quach, Caroline

2017-01-01

ABSTRACT Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. Methods: Before the 2013–2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. Results: Influenza RNA was detected in 16% fewer participants (95% CrI: −7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: −16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: −2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: −0.37, 1.26). Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and −negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference. PMID:28273006

Respiratory muscle training increases respiratory muscle strength and reduces respiratory complications after stroke: a systematic review.

PubMed

Menezes, Kênia Kp; Nascimento, Lucas R; Ada, Louise; Polese, Janaine C; Avelino, Patrick R; Teixeira-Salmela, Luci F

2016-07-01

After stroke, does respiratory muscle training increase respiratory muscle strength and/or endurance? Are any benefits carried over to activity and/or participation? Does it reduce respiratory complications? Systematic review of randomised or quasi-randomised trials. Adults with respiratory muscle weakness following stroke. Respiratory muscle training aimed at increasing inspiratory and/or expiratory muscle strength. Five outcomes were of interest: respiratory muscle strength, respiratory muscle endurance, activity, participation and respiratory complications. Five trials involving 263 participants were included. The mean PEDro score was 6.4 (range 3 to 8), showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training increased maximal inspiratory pressure by 7 cmH2O (95% CI 1 to 14) and maximal expiratory pressure by 13 cmH2O (95% CI 1 to 25); it also decreased the risk of respiratory complications (RR 0.38, 95% CI 0.15 to 0.96) compared with no/sham respiratory intervention. Whether these effects carry over to activity and participation remains uncertain. This systematic review provided evidence that respiratory muscle training is effective after stroke. Meta-analyses based on five trials indicated that 30minutes of respiratory muscle training, five times per week, for 5 weeks can be expected to increase respiratory muscle strength in very weak individuals after stroke. In addition, respiratory muscle training is expected to reduce the risk of respiratory complications after stroke. Further studies are warranted to investigate whether the benefits are carried over to activity and participation. PROSPERO (CRD42015020683). [Menezes KKP, Nascimento LR, Ada L, Polese JC, Avelino PR, Teixeira-Salmela LF (2016) Respiratory muscle training increases respiratory muscle strength and reduces respiratory complications after stroke: a systematic review.Journal of Physiotherapy62: 138-144]. Copyright © 2016 Australian

Epidemiological study of people living in rural North Carolina for novel respiratory viruses.

PubMed

Wang, X; Anderson, B D; Pulscher, L A; Bailey, E S; Yondon, M; Gray, G C

2018-02-01

During the last 10 years, scientists have grown increasingly aware that emerging respiratory viruses are often zoonotic in their origin. These infections can originate from or be amplified in livestock. Less commonly recognized are instances when humans have transmitted their respiratory pathogens to animals (reverse zoonoses). Even with this knowledge of viral exchange at the human-livestock interface, few studies have been conducted to understand this cross-over. In this pilot study, we examined persons with influenza-like illness at an outpatient clinic for evidence of infection with novel zoonotic respiratory pathogens in rural North Carolina where there are dense swine and poultry farming. Environmental air sampling was also conducted. From July 2016 to March 2017, a total of 14 human subjects were enrolled and sampled, and 192 bioaerosol samples were collected. Of the 14 human subject samples molecularly tested, three (21.4%) were positive for influenza A, one (7.1%) for influenza B and one (7.1%) for human enterovirus. Of the 192 bioaerosol samples collected and tested by real-time RT-PCR or PCR, three (1.6%) were positive for influenza A and two (1.0%) for adenovirus. No evidence was found for novel zoonotic respiratory viruses. © 2017 Blackwell Verlag GmbH.

Evaluation of porcine reproductive and respiratory syndrome virus replication in laboratory rodents

PubMed Central

Rosenfeld, Paul; Turner, Patricia V.; MacInnes, Janet I.; Nagy, Éva; Yoo, Dongwan

2009-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major cause of economic losses in the swine industry. The disease is widespread worldwide, and so PRRSV-negative pigs are often difficult to find for the study of PRRSV in vivo. To determine if a small animal model could be developed for PRRSV, 3 strains of laboratory rodent were examined for their susceptibility to the virus. No virus replication was detected in BALB/c or SCID (severe combined immunodeficiency) mice after intraperitoneal inoculation. Moderate replication of PRRSV was detected in primary cotton rat lung cell cultures, but no viral replication was detected following intranasal or intraperitoneal inoculation. Following intratracheal inoculation, viral transcripts were detected in the lungs of cotton rats, but only for 1 day. This study indicates that PRRSV replication in common laboratory rodent species is inefficient, and suggests that a rodent model for this virus is not appropriate. PMID:20046635

M Protein-Deficient Respiratory Syncytial Virus (RSV) Vaccine Protects Infant Baboons Against RSV Challenge

PubMed Central

Welliver, Robert C; Oomens, Antonius; Wolf, Roman; Papin, James; Ivanov, Vadim; Preno, Alisha; Staats, Rachel; Piedra, Pedro; Yu, Zhongxin

2017-01-01

Abstract Background RSV bronchiolitis is the most common cause of hospitalization of infants in the US, and may lead to the development of long-term airway disease. Inactivated vaccines may lead to enhanced disease, while replicating vaccines have caused unacceptable degrees of illness, and may revert back to wild type. We developed an RSV vaccine lacking the gene for the M protein (Mnull RSV). The M protein is responsible for reassembly of the virus after it infects cells and expresses its proteins. Infant baboons vaccinated intranasally (IN) with Mnull RSV develop serum neutralizing antibody (NA) responses, but the virus does not replicate. Methods 2-week-old baboons (n = 12) were primed IN with 107 vaccine units of Mnull RSV or a control preparation, and a similar booster dose was given 4 weeks later. Mnull RSV vaccination did not cause tachypnea, airway inflammation or other signs of illness when compared with sham-vaccinated controls. Two weeks after boosting, all infants were challenged intratracheally with human RSV A2. We continuously monitored respiratory rates and levels of overall activity. On various days following challenge, we obtained BAL fluids for leukocyte counts and degree of virus replication, and evaluated alveolar-arterial oxygen gradients (A-a O2). Results Vaccinated animals (vs. unvaccinated controls) had lower respiratory rates (P = 0.0014), improved A-a O2 (P = 0.0063) and reduced viral replication (P = 0.0014). Activity scores were higher in vaccine recipients than in unvaccinated animals. Vaccine recipients also were primed for earlier serum and secretory neutralizing antibody responses, and greater airway lymphocyte responses. Airway lymphocyte numbers (but not antibody responses) were associated with lower respiratory rates and reduced viral replication (P < 0.01). Conclusion Vaccination intranasally with Mnull RSV protected infant baboons against an RSV challenge without causing respiratory disease or enhanced illness, and

[Epidemiological profile of respiratory diseases in children hospitalized at the Rabat Children's Hospital, Morocco].

PubMed

Benchekroun, Ilham; Boubkraoui, Mohamed El Mahdi; Mekaoui, Nour; Karboubi, Lamia; Mahraoui, Chafiq; Dakhama, Badr Sououd Benjelloun

2017-01-01

Respiratory diseases are a common cause of pediatric hospitalization. This study aimed to evaluate the epidemiological profile of respiratory diseases among children at the Rabat Children's Hospital, Morocco. We conducted an observational-cross sectional study of all children aged 3 months to 15 years hospitalized for respiratory disease at the Department of Pneumoallergology and Pediatric Infectious Diseases at the Rabat Children's Hospital, Morocco over a one-year period, from 1 January 2014 to 31 December 2014. Out of 3537 hospitalized patients, 2493 (70.5%) had respiratory disease. Hospitalizations due to asthmatic exacerbation (p < 0.001), acute bronchiolitis (p < 0.001) and laryngeal dyspnoea (p = 0.004) were more frequent among boys, while hospitalizations due to acute pneumonia (p = 0.005), inhalation of a foreign body (p = 0.007) and pertussis (p = 0.020) were frequent among girls. Hospitalizations due to acute pneumonia (p < 0.001), exacerbation of serious viral disease sequelae (p < 0.001) and pertussis (p < 0.001) were more frequent among infants. Hospitalizations due to acute pneumonia (p < 0.001) and pertussis (p = 0.015) were more frequent during the autumn-winter period. The causes of hospitalization were dominated by asthmatic exacerbations and acute bronchiolitis, which were more frequent among boys. Respiratory infections, such as acute pneumonitis and pertussis, were more frequent during the autumn-winter period and mainly affected the infants.

Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production

PubMed Central

Wang, Zeng-yan; Zhong, Ting; Wang, Yue; Song, Feng-mei; Yu, Xiao-feng; Xing, Li-ping; Zhang, Wen-yan; Yu, Jing-hua; Hua, Shu-cheng; Yu, Xiao-fang

2017-01-01

Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of the Picornaviridae family, EV-A71, differs from EV-D68 in that G0/G1 synchronization inhibits, rather than promotes, EV-A71 viral replication. However, these viruses are similar in that G2/M synchronization inhibits the production and activity of both viruses, which is suggestive of a common therapeutic target for both types of enterovirus. These results further clarify the pathogenic mechanisms of enteroviruses and provide a potential strategy for the treatment and prevention of EV-D68-related disease. PMID:28229049

Viral Disease Networks?