Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5–13 Years

Journal of the Pediatric Infectious Diseases Society BRIEF REPORT Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5–13 Years Vanderbilt University Medical Center, Nashville, Tennessee; 2University of Rochester School of Medicine and Dentistry, New York; 3Mattel Children’s Hospital at University of California at Los Angeles; 4Cincinnati Children’s Hospital Medical Center, Ohio; 5 Emory University, Atlanta, Georgia; 6National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and 7University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh of UPMC, Pennsylvania 1 We detected human metapneumovirus (HMPV) in 54 (5%) of 1055 children aged 5 to 13 years with acute respiratory illness (ARI) identified by outpatient and emergency department surveillance between November and May 2003–2009. Its clinical features were similar to those of HMPV-negative ARI, except a diagnosis of pneumonia was more likely (13% vs 4%, respectively; P = .005) and a diagnosis of pharyngitis (7% vs 24%, respectively; P = .005) was less likely in patients with HMPVpositive ARI than those with HMPV-negative ARI. Keywords. acute respiratory illness; human metapneumovirus; older children. Human metapneumovirus (HMPV) is associated with acute respiratory illness (ARI) in both children and adults [1–7]. The spectrum of disease among children can range from mild upper respiratory tract infection to lower respiratory tract involvement that presents as bronchiolitis, croup, or pneumonia [1, 2]. Many studies that have described the characteristics of HMPV infection in children were focused on infants and young children, whereas the burden and clinical features of HMPV infection among older children remain less well defined. Using prospective population-based surveillance data from the Centers for Disease Control and Prevention (CDC)supported New Vaccine Surveillance Network (NVSN), our Received 26 October 2016; editorial decision 17 January 2017; accepted 23 January 2017; published online March 24, 2017. Correspondence: J. V. Williams, MD, Children’s Hospital of Pittsburgh, Division of Pediatric Infectious Diseases, 4401 Penn Ave, Rangos 9122, Pittsburgh, PA 15224 (). Journal of the Pediatric Infectious Diseases Society   2018;7(2):165–8 © The Author(s) 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: . DOI: 10.1093/jpids/pix012 METHODS Study Design Surveillance was conducted in the counties surrounding Cincinnati, Ohio, Nashville, Tennessee, and Rochester, New York, between November and May in 2003–2009. Children aged 5 to 13 years who had an ARI were enrolled from the outpatient department (OPD) 1 or 2 days/week; patients who presented to the ED were enrolled 1 to 4 days/week. ARI was defined as an illness that presented with fever and/or 1 or more of the following symptoms: cough, earache, nasal congestion, rhinorrhea, sore throat, vomiting after coughing, wheezing, and/or labored, rapid, or shallow breathing. Children were excluded if their symptoms were present for >14 days, if they had chemotherapy-associated neutropenia, or if they had been hospitalized within the previous 4 days. Additional details of the NVSN study design have been reported [1, 8]. After informed consent was provided by the parent/guardian, caretakers were interviewed to obtain demographic and clinical information, including underlying medical conditions, presence and duration of symptoms and signs of ARI, and complications of illness. Medical records were also reviewed for clinical and laboratory information. Information on conditions considered to confer higher risk for respiratory illnesses, including premature birth (<36 weeks’ gestation), chronic pulmonary disease (including asthma), cardiac, renal, or immunodeficiency disease, cancer, or sickle cell anemia, was also obtained. Nasal and throat swabs were also obtained from each child for virologic testing [8]. After the enrollment visit, the medical records for each encounter were reviewed and recorded; the information we captured included International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis codes assigned by the respective medical center’s professional coders. Laboratory Testing Nasal and throat swabs were combined into a tube of transport medium and delivered at ambient temperature within 1 to 2 hours to the research virology laboratory at each site. For HMPV testing by reverse-transcription polymerase chain reaction (RT-PCR), sample aliquots were collected in lysis buffer and frozen at −70°C until shipped in batches to Vanderbilt BRIEF REPORT • JPIDS 2018:7 (June) • 165 Leigh M. Howard,1 Kathryn M. Edwards,1 Yuwei Zhu,1 Marie R. Griffin,1 Geoffrey A. Weinberg,2 Peter G. Szilagyi,3 Mary A. Staat,4 Daniel C. Payne,5,6 and John V. Williams7 group previously described the clinical features associated with HMPV infection in young children in inpatient and outpatient settings [1]. Here, we analyze data from older children (aged 5–13 years) who presented to an outpatient facility (outpatient clinic or emergency department [ED]) for medical attention to define the clinical features and etiologic role of HMPV in this age group. University for RNA extraction and real-time RT-PCR [1]. The RT-PCR assay was designed using a dual-labeled fluorescent probe targeting the nucleoprotein (N) gene and was capable of detecting <50 RNA copies per reaction. Samples were also tested for the presence of respiratory syncytial virus (RSV) and influenza. Details of the laboratory methods were described previously [9]. Statistical Analysis RESULTS A total of 1055 children aged 5 to 13 years with ARI were enrolled and provided respiratory samples; 54 (5.1%) of them tested positive for HMPV (Table 1). In 48 (88.9%) of these 54 cases, HMPV was the only virus detected, whereas RSV was detected with HMPV in 4 (7.4%) of the 54, and influenza was codetected in 2 (3.7%) of the 54. The median age of these older ambulatory children with HMPV infection was 7 years (interquartile Table 1. Clinical Features of HMPV Infection in Children Aged 5–13 Yearsa Feature HMPV-Positive Group (n = 54) HMPV-Negative Group (n = 1001) Total (n = 1055) Pb 84.0 (72.8–114.8) 92.0 (73.0–117.0) 92.0 (73.0–118.0) .435   Female 25 (46) 488 (49) 513 (49)   Male 29 (54) 513 (51) 542 (51)   Black 22 (41) 542 (54) 564 (53)   White 13 (24) 202 (20) 215 (20)   Hispanic 13 (24) 168 (17) 181 (17)   Other 6 (11) 88 (9) 94 (9)   Unknown 0 (0) 1 (0) 1 (0) High-risk preexisting conditionc 26 (48) 447 (45) 473 (45) .615 Child born >1 mo early (N = 68) (n [%]) 1 (25) 14 (23) 15 (23) .964 Cough 53 (98) 848 (85) 901 (85) .006 Shortness of breath 27 (50) 407 (41) 434 (41) .339 Earache 12 (22) 261 (25) 273 (26) .589 Sore t (...truncated)