Original Article

Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children Helen Y. Chu,1 Christian Renaud,2 Elle Ficken,2 Blythe Thomson,3 Jane Kuypers,4 and Janet A. Englund2 1

Department of Medicine, University of Washington, 2Division of Infectious Diseases, 3Division of Hematology-Oncology, Seattle Children’s Hospital; and 4Department of Laboratory Medicine, University of Washington, Seattle

Corresponding Author: Helen Y. Chu, MD, MPH, Division of Allergy & Infectious Diseases, 1616 Eastlake Ave E. Suite 320, Seattle, WA 98102. E-mail: [email protected]. H. Y. C. and C. R. are joint first authors. Received August 2, 2012; accepted October 16, 2012; electronically published October 21, 2014.

Background. The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. Methods. We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher’s exact tests. Results. Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen 28% FiO2. Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. Conclusions. Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation. Key words.

human metapneumovirus; immunocompromised; pediatric; transplant; treatment.

BACKGROUND Human metapneumovirus (hMPV) is a paramyxovirus first identified in 2001 as a pathogen associated with upper and lower respiratory tract infections in children [1]. Seroprevalence studies show that almost all children acquire infection by 5 years of age, and that frequent reinfections occur through life [2, 3]. The prevalence of hMPV infection among hospitalized children with acute respiratory infection or fever is similar to that of other respiratory viruses. Clinical disease most closely resembles that associated with respiratory syncytial virus infection (RSV), a related paramyxovirus [4]. A prospective cohort study of hMPV revealed a 9.4% seroprevalence in children hospitalized with respiratory tract infections, with 63% of patients requiring supplemental oxygen and 3% requiring intensive care unit (ICU) admission [5]. Lower respiratory

tract illnesses (LRTI) caused by hMPV includes bronchiolitis, pneumonia, and croup. hMPV is also associated with acute otitis media, as well as more rarely conjunctivitis, gastroenteritis, and rash [6, 7]. In adults with hematologic malignancy, hMPV is associated with high rates of progression from upper to lower respiratory tract disease and substantial mortality [8, 9]. The treatment of hMPV is mainly supportive. Animal data support the use of bronchodilators and corticosteroids, but no controlled trials have been done to assess their efficacy in human populations [10]. Ribavirin is a nucleoside analogue shown in in-vitro studies to have activity against hMPV [11]. Ribavirin is approved for use in treatment of respiratory syncytial virus (RSV), and is often used in combination with intravenous immunoglobulin (IVIG) in severely immunocompromised individuals. Few prior

Journal of the Pediatric Infectious Diseases Society, Vol. 3, No. 4, pp. 286–93, 2014. DOI:10.1093/jpids/piu100 © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/ licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact [email protected]

Human Metapneumovirus in Immunocompromised Children

descriptions of the clinical management and treatment of hMPV respiratory tract infections in a pediatric immunocompromised population, including children with leukemia and solid organ transplant recipients, are available. We describe hMPV respiratory tract infections in 55 pediatric immunocompromised patients at Seattle Children’s Hospital, reporting on their clinical presentation, management, and outcomes.

METHODS Screening of all positive laboratory results for hMPV by both direct fluorescent antibody (DFA) and real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) was performed to identify patients between the ages of newborn to 19 years who were diagnosed at Seattle Children’s Hospital in Seattle, WA during the years 2006–2010. Of 368 total patients with positive hMPV laboratory results, we performed retrospective chart review to identify a subset of 55 patients with immunocompromised conditions. We defined an immunocompromised condition as presence of hematologic malignancy, solid tumor, rheumatologic disease receiving immunosuppressive therapy, solid organ transplant, primary immunodeficiency, receipt of chronic immunosuppressive therapy, or receipt of a hematopoietic stem cell transplant (HSCT). Using electronic chart review, we abstracted sociodemographic variables, symptoms, laboratory and radiologic values, clinical course, and treatment outcomes for these patients. Respiratory specimens were obtained by nasal washes for patients with suspected respiratory viral infections by attending physicians, or from bronchoalveolar lavage fluid (BAL) when this was performed. DFA was performed using virus-specific mouse monoclonal antibodies (Chemicon, Temecula, CA), and RT-qPCR was performed using previously published methods at the University of Washington Virology Laboratories [12]. Viral load values were obtained on a subset of patients whose samples were tested by RT-qPCR. Estimated viral load data were calculated from cycle threshold values on RT-qPCR analysis using stored standard curve data for hMPV. Upper respiratory tract infection (URTI) was defined as hMPV documented in an upper respiratory tract specimen in a patient with compatible symptoms in the absence of radiographic or clinical evidence of pneumonia. LRTI was defined as a new pulmonary infiltrate or presence of lower respiratory tract symptoms (wheezing or hypoxia) in association with a positive lower respiratory tract specimen or a positive upper respiratory tract specimen if the patient did not undergo BAL. Neutropenia was defined as absolute neutrophil count

Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children.

The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood...
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