Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients

ABSTRACTRATIONALECurrent microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies.OBJECTIVESTo address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses.METHODSWe enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays.MEASUREMENTS & MAIN RESULTSmNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus,Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A,Corynebacterium propinquumandStreptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017).CONCLUSIONSCompared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.

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Evaluation of Human Respiratory Syncytial Virus and Human Parainfluenza Virus Type 3 among Hospitalized Children in Northwest of Iran

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2021/2270307 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Zahra Ramezannia ◽

Javid Sadeghi ◽

Shahram Abdoli Oskouie ◽

Mohammad Ahangarzadeh Rezaee ◽

Hossein Bannazadeh Baghi ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Respiratory Infections ◽

Winter Season ◽

Human Respiratory Syncytial Virus ◽

Respiratory Pathogens ◽

Limited Information ◽

Syncytial Virus ◽

Tract Infections

Background. Acute respiratory tract infections (ARTIs) are the leading cause of illnesses in children. Human respiratory syncytial virus (HRSV) and human parainfluenza viruses (HPIVs) are among the most common etiologic agents associated with viral respiratory tract infections in children worldwide. Nevertheless, limited information is available on the spread of infections of these two viruses in northwest Iran. Objective. The purpose of the current study is to evaluate the frequency of RSV and HPIV-3 and clinical features among Iranian children with confirmed respiratory infections between April 2019 and March 2020. Methods. 100 nasopharyngeal swabs were collected from hospitalized patients (under 5 years old) with ARTI from Tabriz Children’s Hospital. Detection of respiratory viruses was performed using the nested RT-PCR method. Results. Respiratory syncytial virus and HPIV-3 were recognized in 18% (18/100) and 2% (2/100) of children, respectively. Ten (55.6%) of the RSV-positive samples were male, while 8 (44.4%) were female. HPIV‐3 was found only among 2 male patients (100%). Most patients (61.1%) with RSV infection were less than 12 months old. Additionally, samples that were positive for HPIV-3 were less than 12 months old. RSV infections had occurred mainly during the winter season. Conclusions. This study confirms that RSV can be one of the important respiratory pathogens in children in northwestern Iran. However, according to this study, HPIV-3 has a lower prevalence among children in this area than RSV. Therefore, implementing a routine diagnosis for respiratory pathogens can improve the management of respiratory infections in children.

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Role of Respiratory Syncytial Virus in Pediatric Pneumonia

Microorganisms ◽

10.3390/microorganisms8122048 ◽

2020 ◽

Vol 8 (12) ◽

pp. 2048

Author(s):

Sonia Bianchini ◽

Ettore Silvestri ◽

Alberto Argentiero ◽

Valentina Fainardi ◽

Giovanna Pisi ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Young Children ◽

Respiratory Infections ◽

Clinical Signs ◽

Supportive Therapy ◽

Respiratory Pathogens ◽

Single Polymerase Chain Reaction ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.

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Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

Microorganisms ◽

10.3390/microorganisms9061293 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1293

Author(s):

Gaspar A. Pacheco ◽

Nicolás M. S. Gálvez ◽

Jorge A. Soto ◽

Catalina A. Andrade ◽

Alexis M. Kalergis

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A ◽

Human Respiratory Syncytial Virus ◽

Respiratory Pathogens ◽

Parainfluenza Viruses ◽

Starting Point ◽

The Social ◽

Syncytial Virus ◽

Tract Infections ◽

Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

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Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

BMC Infectious Diseases ◽

10.1186/s12879-021-05996-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Cheng Lei ◽

Lisong Yang ◽

Cheong Tat Lou ◽

Fan Yang ◽

Kin Ian SiTou ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Pediatric Patients ◽

Respiratory Infections ◽

Upper Respiratory Tract ◽

Viral Etiology ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

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Prescription Surveillance and Polymerase Chain Reaction Testing to Identify Pathogens during Outbreaks of Infection

BioMed Research International ◽

10.1155/2013/746053 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Hiroaki Sugiura ◽

Tsuguto Fujimoto ◽

Tamie Sugawara ◽

Nozomu Hanaoka ◽

Masami Konagaya ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Syndromic Surveillance ◽

Respiratory Infections ◽

Emerging Infectious Diseases ◽

Upper Respiratory Tract ◽

Chain Reaction ◽

Specific Pathogen ◽

Polymerase Chain ◽

Syncytial Virus ◽

Tract Infections

Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses andMycoplasma pneumoniae. Infectious agents includingM. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak ofM. pneumoniaeinfection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.

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Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽

10.3390/pathogens11010047 ◽

2021 ◽

Vol 11 (1) ◽

pp. 47

Author(s):

Catalina A. Andrade ◽

Alexis M. Kalergis ◽

Karen Bohmwald

Keyword(s):

Respiratory Syncytial Virus ◽

Viral Infections ◽

Respiratory Infections ◽

The Elderly ◽

Cell Types ◽

Potential Effect ◽

Viral Agent ◽

Pulmonary Manifestations ◽

Syncytial Virus ◽

Tract Infections

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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Respiratory syncytial virus and airway microbiota -- A complex interplay and its reflection on morbidity

10.22541/au.160638847.70128113/v1 ◽

2020 ◽

Author(s):

Giovanni Rossi ◽

Stefania Ballarini ◽

Michela Silvestri ◽

Oliviero Sacco ◽

Andrew Colin

Keyword(s):

Respiratory Syncytial Virus ◽

Disease Severity ◽

Respiratory Infections ◽

Pediatric Population ◽

Bacterial Species ◽

Severe Disease ◽

Microbial Community Composition ◽

Positive Role ◽

Syncytial Virus ◽

Tract Infections

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

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Respiratory tract viruses

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0076_update_001 ◽

2020 ◽

pp. 723-734

Author(s):

Malik Peiris

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Infections ◽

Influenza Viruses ◽

Parainfluenza Viruses ◽

Clinical Syndromes ◽

Respiratory Tract Viruses ◽

Syncytial Virus ◽

Tract Infections ◽

Viral Respiratory Infections

Viral respiratory infections, including coronavirus, rhinovirus, adenovirus, respiratory syncytial virus, human metapneumovirus, parainfluenza viruses, and influenza viruses, are a substantial cause of morbidity and mortality worldwide, most notably the COVID-19 pandemic. Transmission occurs through direct contact, contaminated fomites, and large airborne droplets, with long-range transmission by small particle aerosols reported in at least some instances of influenza and severe acute respiratory syndrome. Clinical syndromes affect the upper and/or lower respiratory tract, including coryza, pharyngitis, croup, bronchiolitis, and pneumonia. Each syndrome can potentially be caused by several viruses, and each respiratory virus can be associated with different clinical syndromes. Measles is a major cause of lower respiratory tract infections and fatality in tropical countries.

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WU Polyomavirus Associated with Severe Respiratory Failure in Children

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.744 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S317-S318

Author(s):

Kazuhiro Uda ◽

Kensuke Shoji ◽

Chitose Wakai-Koyama ◽

Isao Miyairi

Keyword(s):

Respiratory Failure ◽

Respiratory Tract ◽

Respiratory Infections ◽

Underlying Disease ◽

Respiratory Pathogens ◽

Immunocompromised Patients ◽

Severe Respiratory Failure ◽

Preterm Children ◽

Wu Polyomavirus ◽

Tract Infections

Abstract Background WU polyomavirus (WUPyV) is a relatively new virus associated with respiratory infections. However, its role is unclear in children with severe respiratory failure. We aimed to evaluate characteristics of severe respiratory failure associated with WUPyV in children. Methods We retrospectively reviewed the cases of respiratory tract infection at a tertiary children’s hospital in Tokyo between April 2010 and April 2017. We performed real-time polymerase chain reaction (PCR) for WUPyV using residual extracted nucleic acid samples taken from respiratory tract samples of pediatric patients, primarily with respiratory failure. We investigated the clinical characteristics of patients positive for WUPyV. Samples positive for WUPyV were evaluated for co-infection with fast-track diagnostic kit (FTD-2); a multiplex PCR capable of detecting 21 respiratory pathogens. Results WUPyV was detected in 14 among 318 samples obtained from respiratory tract infections. Median age was 34 months old and males were predominant (n = 11, 64%). Underlying disease was found in 11 (79%) cases, including five cases of preterm children and three immunocompromised patients. The most common clinical diagnosis was pneumonia (n = 13, 93%). Majority of the respiratory samples were endotracheal tube aspirates (n = 11, 79%) and the remaining were nasopharyngeal swabs. Co- infection was found in eight (57%) cases. WUPyV was the only pathogen detected in six cases, including two preterm children and one immunocompromised patient. Nine cases required mechanical ventilation, and two cases required extracorporeal membrane oxygenation (ECMO). Conclusion WUPyV was detected from children with severe respiratory failure due to pneumonia, independently or concurrently with other pathogens, especially in preterm and immunocompromised patients. Disclosures All authors: No reported disclosures.

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Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

European Respiratory Journal ◽

10.1183/09031936.00085614 ◽

2014 ◽

Vol 45 (3) ◽

pp. 718-725 ◽

Cited By ~ 14

Author(s):

Corné H. van den Kieboom ◽

Inge M.L. Ahout ◽

Aldert Zomer ◽

Kim H. Brand ◽

Ronald de Groot ◽

...

Keyword(s):

Gene Expression ◽

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Pathogen Detection ◽

Severe Disease ◽

Host Gene ◽

Host Gene Expression ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.

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