Comparison of Risk Factors for Human Metapneumovirus and Respiratory Syncytial Virus Disease Severity in Young Children

Abstract Background. Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading pediatric pathogens. However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections. Methods. We studied a prospective cohort of >1000 children aged <3 years hospitalized in or presenting to a pediatric clinic for acute respiratory infection. We collected clinical data at enrollment and 1-month follow-up and tested nasopharyngeal secretions for respiratory viruses. Disease severity was defined as hospitalization and was also assessed with a severity score (1 point/variable) calculated on the basis of fraction of inhaled O2 ≥ 30%, hospitalization >5 days, and pediatric intensive care unit admission. Results. hMPV was identified in 58 of 305 outpatient children (19.0%) and 69 of 734 hospitalized children (9.4%), second only to RSV (48.2% and 63.6%, respectively). In multivariate regression analysis of hMPV cases, age <6 months and household crowding were associated with hospitalization. Among hospitalized patients, risk factors for severe hMPV disease were female sex, prematurity, and genotype B infection. Age <6 months, comorbidities, and household crowding were risk factors for RSV hospitalization; breast-feeding and viral coinfection were protective. Age <6 months and prematurity were associated with severe RSV cases among hospitalized children. Conclusions. hMPV and RSV severity risk factors may differ slightly. These findings will inform hMPV prevention strategies.

[1]  Bernhard Resch,et al.  Burden of respiratory syncytial virus infection in young children. , 2012, World journal of clinical pediatrics.

[2]  A. Wald,et al.  Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children , 2011, Influenza and other respiratory viruses.

[3]  R. Peebles,et al.  Differential Pathogenesis of Respiratory Syncytial Virus Clinical Isolates in BALB/c Mice , 2011, Journal of Virology.

[4]  Rafia Bhore,et al.  Risk Factors in Children Hospitalized With RSV Bronchiolitis Versus Non–RSV Bronchiolitis , 2010, Pediatrics.

[5]  P. Kiener,et al.  Prophylactic and therapeutic benefits of a monoclonal antibody against the fusion protein of human metapneumovirus in a mouse model. , 2010, Antiviral research.

[6]  G. Boivin,et al.  The distinguishing features of human metapneumovirus and respiratory syncytial virus , 2010, Reviews in medical virology.

[7]  P. Szilagyi,et al.  Population-Based Incidence of Human Metapneumovirus Infection among Hospitalized Children , 2010, The Journal of infectious diseases.

[8]  S. Madhi,et al.  Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis , 2010, The Lancet.

[9]  Lucia H. Lee,et al.  Modified Recommendations for Use of Palivizumab for Prevention of Respiratory Syncytial Virus Infections , 2009, Pediatrics.

[10]  D. Greenberg,et al.  Association of Human Metapneumovirus with Radiologically Diagnosed Community-Acquired Alveolar Pneumonia in Young Children , 2009, The Journal of Pediatrics.

[11]  Jacques Corbeil,et al.  Comparison of Automated Microarray Detection with Real-Time PCR Assays for Detection of Respiratory Viruses in Specimens Obtained from Children , 2009, Journal of Clinical Microbiology.

[12]  M. Bubenheim,et al.  In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses , 2009, PloS one.

[13]  M. Bergeron,et al.  Infection with Human Metapneumovirus Predisposes Mice to Severe Pneumococcal Pneumonia , 2008, Journal of Virology.

[14]  G. Boivin,et al.  Identification and Evaluation of a Highly Effective Fusion Inhibitor for Human Metapneumovirus , 2007, Antimicrobial Agents and Chemotherapy.

[15]  G. Cilla,et al.  Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  Alan D. Lopez,et al.  Global burden of disease and risk factors , 2006 .

[17]  M. Holtzman,et al.  Genetic variability of human metapneumovirus infection: evidence of a shift in viral genotype without a change in illness. , 2006, The Journal of infectious diseases.

[18]  J. Devincenzo,et al.  Factors Predicting Childhood Respiratory Syncytial Virus Severity: What They Indicate About Pathogenesis , 2005, The Pediatric infectious disease journal.

[19]  P. Shears,et al.  Dual Infection of Infants by Human Metapneumovirus and Human Respiratory Syncytial Virus Is Strongly Associated with Severe Bronchiolitis , 2005, The Journal of infectious diseases.

[20]  Ian Mitchell,et al.  The Pediatric Investigators Collaborative Network on Infections in Canada Study of Predictors of Hospitalization for Respiratory Syncytial Virus Infection for Infants Born at 33 Through 35 Completed Weeks of Gestation , 2004, The Pediatric infectious disease journal.

[21]  J. Crowe,et al.  Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. , 2004, The New England journal of medicine.

[22]  M. Bergeron,et al.  Human Metapneumovirus Infections in Hospitalized Children , 2003, Emerging infectious diseases.

[23]  T. Kuiken,et al.  A newly discovered human pneumovirus isolated from young children with respiratory tract disease , 2001, Nature Medicine.

[24]  R. Holman,et al.  Bronchiolitis-associated hospitalizations among US children, 1980-1996. , 1999, JAMA.

[25]  E. Wang,et al.  Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. , 1995, The Journal of pediatrics.

[26]  R. Fouchier,et al.  Vaccination approaches to combat human metapneumovirus lower respiratory tract infections. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[27]  M. Bergeron,et al.  Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons. , 2006, The Journal of infectious diseases.

[28]  Alan D. Lopez,et al.  The Burden of Disease and Mortality by Condition: Data, Methods, and Results for 2001 -- Global Burden of Disease and Risk Factors , 2006 .

[29]  P. Stang,et al.  The economic burden of respiratory syncytial virus-associated bronchiolitis hospitalizations. , 2001, Archives of pediatrics & adolescent medicine.

[30]  W. Ambrosius,et al.  Forced expiratory flows and volumes in infants. Normative data and lung growth. , 2000, American journal of respiratory and critical care medicine.

[31]  Y. Gillet -Prevention of respiratory syncytial virus infection-. , 1998, Archives de pediatrie : organe officiel de la Societe francaise de pediatrie.