Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations

Abstract Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. Methods Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression. Results HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43–9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59–.99) and atypical (OR, 0.39; 95% CI, .19–.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55–1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87–7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32–2.50) were more severe than HMPV (reference), but all other pathogens had similar severity. Conclusions Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.

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Parainfluenza Virus Types 1–3 Infections Among Children and Adults Hospitalized With Community-acquired Pneumonia

Clinical Infectious Diseases ◽

10.1093/cid/ciaa973 ◽

2020 ◽

Author(s):

Leigh M Howard ◽

Kathryn M Edwards ◽

Yuwei Zhu ◽

Derek J Williams ◽

Wesley H Self ◽

...

Keyword(s):

Clinical Features ◽

Bacterial Pneumonia ◽

Pathogen Detection ◽

Multivariable Analysis ◽

Population Based ◽

Community Acquired Pneumonia ◽

Parainfluenza Virus ◽

Ordinal Scale ◽

Active Population ◽

Tract Infections

Abstract Background Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia. Methods We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression. Results PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88–37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens. Conclusions Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.

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Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy061 ◽

2018 ◽

Vol 5 (4) ◽

Cited By ~ 2

Author(s):

Catherine H Bozio ◽

W Dana Flanders ◽

Lyn Finelli ◽

Anna M Bramley ◽

Carrie Reed ◽

...

Keyword(s):

Multiple Imputation ◽

Population Based ◽

Community Acquired Pneumonia ◽

Influenza Viruses ◽

Absolute Difference ◽

Respiratory Illnesses ◽

Active Population ◽

Syncytial Virus ◽

Using Data ◽

Relative Differences

Abstract Background Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. Methods Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1–3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. Results Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%–4.4% and 0.8%–2.8% in children and adults, respectively; relative differences were 1.1–3.0 times higher. Conclusions Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.

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Analysis of Clinical Features of Community-acquired Pneumonia Caused by Pediatric Respiratory Syncytial Virus and Human Metapneumovirus

Kansenshogaku zasshi ◽

10.11150/kansenshogakuzasshi.84.42 ◽

2010 ◽

Vol 84 (1) ◽

pp. 42-47 ◽

Cited By ~ 3

Author(s):

Takafumi OKADA ◽

Keita MATSUBARA ◽

Takahiro MATSUSHIMA ◽

Osamu KOMIYAMA ◽

Keiko HAMANO (HASEGAWA) ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Clinical Features ◽

Community Acquired Pneumonia ◽

Human Metapneumovirus ◽

Syncytial Virus

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Human Metapneumovirus: Etiological Agent of Severe Acute Respiratory Infections in Hospitalized and Deceased Patients with a Negative Diagnosis of Influenza

Pathogens ◽

10.3390/pathogens9020085 ◽

2020 ◽

Vol 9 (2) ◽

pp. 85

Author(s):

Gisela Barrera-Badillo ◽

Beatriz Olivares-Flores ◽

Adriana Ruiz-López ◽

Miguel Ángel Fierro-Valdez ◽

Rosaura Idania Gutiérrez-Vargas ◽

...

Keyword(s):

Young Children ◽

Age Groups ◽

Simultaneous Detection ◽

Respiratory Viruses ◽

Human Metapneumovirus ◽

Late Winter ◽

Older Individuals ◽

Severe Acute Respiratory Infection ◽

Syncytial Virus ◽

Tract Infections

Human metapneumovirus (HMPV) is one of the four major viral pathogens associated with acute respiratory tract infections (ARI) and creates a substantial burden of disease, particularly in young children (<5 years) and older individuals (≥65 years). The objective of this study was to determine the epidemiological behavior of HMPV in Mexico. This retrospective study was conducted over a nine-year period and used 7283 influenza-negative respiratory samples from hospitalized and deceased patients who presented Severe Acute Respiratory Infection (SARI). The samples were processed with the help of qualitative multiplex RT-PCR for simultaneous detection of 14 respiratory viruses (xTAG® RVP FAST v2). 40.8% of the samples were positive for respiratory viruses, mainly rhinovirus/enterovirus (47.6%), respiratory syncytial virus (15.9%), HMPV (11.1%) and parainfluenza virus (8.9%). Other respiratory viruses and co-infections accounted for 16.5%. HMPV infects all age groups, but the most affected group was infants between 29 days and 9 years of age (65.6%) and adults who are 40 years and older (25.7%). HMPV circulates every year from November to April, and the highest circulation was observed in late winter. The results of this study aim to raise awareness among clinicians about the high epidemiological impact of HMPV in young children and older individuals in order to reduce the economic burden in terms of health care costs.

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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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Detection of the Human Metapneumovirus and Its Comparison with the Respiratory Syncytial Virus in Malignant Pediatric Patients with Acute Respiratory Tract Infections

The Egyptian Journal of Medical Microbiology ◽

10.12816/0036988 ◽

2016 ◽

Vol 25 (2) ◽

pp. 7-11

Author(s):

Marie A. Marie ◽

Iman E. Wali ◽

Mohamed F. Ibrahim

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Pediatric Patients ◽

Human Metapneumovirus ◽

Acute Respiratory Tract Infections ◽

Syncytial Virus ◽

Tract Infections

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Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients

10.1101/102798 ◽

2017 ◽

Cited By ~ 3

Author(s):

C Langelier ◽

MS Zinter ◽

K Kalantar ◽

GA Yanik ◽

S Christenson ◽

...

Keyword(s):

Pathogen Detection ◽

Respiratory Infections ◽

Human Herpesvirus ◽

Microbial Pathogens ◽

Respiratory Pathogens ◽

Metagenomic Sequencing ◽

Respiratory Illnesses ◽

Standard Testing ◽

Syncytial Virus ◽

Tract Infections

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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Identification and Evaluation of a Highly Effective Fusion Inhibitor for Human Metapneumovirus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00793-07 ◽

2007 ◽

Vol 52 (1) ◽

pp. 279-287 ◽

Cited By ~ 43

Author(s):

Céline Deffrasnes ◽

Marie-Ève Hamelin ◽

Gregory A. Prince ◽

Guy Boivin

Keyword(s):

Fusion Protein ◽

Clinical Symptoms ◽

Pulmonary Inflammation ◽

Human Metapneumovirus ◽

Heptad Repeat ◽

Elderly Subjects ◽

Monocyte Chemoattractant Protein 1 ◽

Syncytial Virus ◽

Tract Infections

ABSTRACT Human metapneumovirus (hMPV) can cause acute upper and lower respiratory tract infections that are particularly severe in young children, elderly subjects, and immunocompromised patients. To date, no treatments or vaccines are available for hMPV infections. Our objective was to assess the inhibitory potential of several peptides derived from the heptad repeat A and B (HRA and HRB) domains of the hMPV fusion protein. Nine candidate peptides were expressed in Escherichia coli or obtained synthetically and tested in vitro and in an animal model. Excellent in vitro inhibition of an hMPV strain of the A1 subgroup was obtained with five peptides, with 50% inhibitory concentrations ranging from 1.4 nM to 3.3 μM. One peptide, HRA2, displayed very potent activity against all four hMPV subgroups. It was also moderately active against human respiratory syncytial virus (strain A2) but displayed no activity against human parainfluenza virus type 3. BALB/c mice that received the HRA2 peptide and a lethal hMPV intranasal challenge simultaneously were completely protected from clinical symptoms and mortality. On day 5 postinfection, HRA2-treated mice had undetectable lung viral loads which were significantly less than those of untreated mice (3 × 104 50% tissue culture infective doses/lung). Pulmonary inflammation, levels of proinflammatory cytokines/chemokines (RANTES, gamma interferon, and monocyte chemoattractant protein 1) and airway obstruction were also significantly decreased in HRA2-treated mice. The results of this study demonstrate that potent antivirals can be derived from the hMPV fusion protein HR domains. Moreover, hMPV, compared to other paramyxoviruses and to the human immunodeficiency virus, seems to be more susceptible to HRA- than HRB-derived peptides.

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Hospitalization rates for human metapneumovirus infection among 0- to 3-year-olds in Gipuzkoa (Basque Country), Spain

Epidemiology and Infection ◽

10.1017/s0950268808000666 ◽

2008 ◽

Vol 137 (1) ◽

pp. 66-72 ◽

Cited By ~ 15

Author(s):

G. CILLA ◽

E. OÑATE ◽

E. G. PEREZ-YARZA ◽

M. MONTES ◽

D. VICENTE ◽

...

Keyword(s):

Incidence Rate ◽

Basque Country ◽

Length Of Hospital Stay ◽

Population Based ◽

Human Metapneumovirus ◽

Respiratory Pathogen ◽

Parainfluenza Viruses ◽

Hospitalization Rates ◽

Hmpv Infection ◽

Syncytial Virus

SUMMARYNumerous studies have been published on human metapneumovirus (HMPV) infection, but few have been population based. The main aim of this study was to estimate the incidence rate of hospitalization for community-acquired HMPV infection in infants and children aged <3 years. Between July 2004 and June 2007, 796 episodes (742 patients) of community-acquired acute respiratory infection were hospitalized. HMPV was detected in 90 episodes (11·3%). Fifty-nine episodes occurred in infants aged <1 year. The mean length of hospital stay was 6·2 days (range 2–31 days). Thirteen children required admission to the intensive care unit. Viral co-infections were detected in 46 episodes (51·1%). The incidence rate of hospitalization per 1000 inhabitants was 2·6 (95% CI 2·1–3·2), lower than that for respiratory syncytial virus, but higher than that observed for the influenza and parainfluenza viruses. HMPV is a major respiratory pathogen that leads to a high hospitalization rate.

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