ORIGINAL STUDIES Clinical Presentation and Severity of Viral Community-Acquired Pneumonia in Young Nepalese Children Maria Mathisen, MD,* Tor A. Strand, PhD,*†‡ Biswa N. Sharma, BSc,§ Ram K. Chandyo, MD,¶ Palle Valentiner-Branth, PhD, Sudha Basnet, MD,¶ Ramesh K. Adhikari, MD,¶ Dag Hvidsten, MD,** Prakash S. Shrestha, MD,¶ and Halvor Sommerfelt, PhD*‡ Background: Most deaths from pneumonia in children 5 years of age occur in developing countries, where information about the clinical impact and severity of viral causes of respiratory infections is limited. Methods: From June 29, 2004 to June 30, 2007 we evaluated 2230 cases of pneumonia (World Health Organization criteria) in children aged 2 to 35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each case was examined for 7 respiratory viruses using reverse-transcription poly- merase chain reaction. We compared illness duration, severity, and treat- ment failure between cases positive and negative for the individual viruses in multiple regression models. Results: A total of 2219 cases had a valid polymerase chain reaction result and were included in the analyses. Overall, 46.1% of cases were 2 to 11 months of age. Being infected with respiratory syncytial virus (RSV) was associated with lower chest indrawing (odds ratio OR 2.17; 95% confi- dence interval CI 1.42–3.30) and, among infants, oxygen saturation 93% (OR: 1.88; CI: 1.32–2.69). Among the 2088 nonsevere pneumonia cases, those positive for RSV had a longer time to recovery (hazard ratio 0.82; CI 0.75– 0.90; P  0.001) and an increased risk of treatment failure (OR: 1.75; CI: 1.34 –2.28; P  0.001) than the RSV negative cases. Conclusions: Being infected with RSV was associated with a more severe clinical presentation of pneumonia, longer illness duration, and increased risk of treatment failure. The severity of RSV infection was age related, infants being more severely affected. Key Words: respiratory viruses, respiratory syncytial virus, parainfluenza virus, influenza virus, human metapneumovirus, lower respiratory tract infection, polymerase chain reaction, developing country (Pediatr Infect Dis J 2010;29: e1– e6) I t is estimated that about 19% of all deaths in children less than 5 years of age are caused by pneumonia and that most of these deaths occur in developing countries. 1 Prospective hospital-based studies suggest that Streptococcus pneumoniae, Haemophilus in- fluenzae, and respiratory syncytial virus (RSV) are the leading causes of childhood pneumonia. 1,2 It is usually not possible to distinguish bacterial from viral disease based on clinical signs or radiographic findings in children. 3 Respiratory viruses are an important cause of childhood illness and a major reason for hospitalization of young children globally. 4,5 RSV causes severe lower respiratory tract infection (LRTI), including bronchiolitis and pneumonia, in infants and young children. 6 Based on available data, the global annual infec- tion and death figures for RSV are estimated to be 64 million and 160,000, respectively. 5 The relative importance of the individual respiratory viruses in young children is best documented in industrialized coun- tries, while there is lack of data from low and middle-income countries. Furthermore, most reports focus on severe pneumonia in hospitalized children, while the nonsevere, but much more com- mon, pneumonias also contribute substantially to the overall bur- den of respiratory illness in children. 7 We have previously identified common viral pathogens in nasopharyngeal aspirate from 2219 community-acquired pneumo- nia (CAP) cases in Nepalese children 2 to 35 months of age visiting a field clinic. 8 Using polymerase chain reaction (PCR) we identified 919 virus isolates in 887 (40.0%) cases during a 3-year period, of which 334 (15.1%) yielded RSV, 164 (7.4%) influenza A, 129 (5.8%) parainfluenza (PIV) type 3, 98 (4.4%) PIV type 1, 93 (4.2%) human metapneumovirus (hMPV); 84 (3.8%) influenza B, and 17 (0.8%) PIV type 2. The main objective of the current report is to describe clinical characteristics, illness duration, and the risk of treatment failure of CAP associated with these 7 respiratory viruses. SUBJECTS AND METHODS Study Area Study participants were recruited from the Bhaktapur dis- trict in the Kathmandu Valley, Nepal. A total of 1913 (86.2%) of the 2219 cases were included from within Bhaktapur municipality; a semi-urban agricultural based town with a population of approx- imately 80,000, of whom we had approximately 4500 children 2 to 35 months of age under monthly surveillance. Malnutrition, mainly manifested as stunting, and anemia are common among children less than 5 years of age. 9 Study Subjects and Case Definition We recruited cases from an open cohort of children less than 3 years of age, who were under monthly active surveillance for respiratory illness. Trained fieldworkers referred children with respiratory complaints to the study clinic at the outpatient depart- ment at Siddhi Memorial Hospital in Bhaktapur. The population Accepted for publication September 22, 2009. From the *Centre for International Health, University of Bergen, Bergen, Norway; †Department of Laboratory Medicine, Medical Microbiology, Sykehuset Innlandet Lillehammer, Norway; ‡Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway; §Department of Micro- biology, Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu Nepal; ¶Child Health Department, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal; Statens Serum Institut, Department of Epidemiology, Division of Epidemiology, Copenhagen, Denmark; and **Department of Mi- crobiology and Infection Control, University Hospital of North Norway, Tromsø, Norway. Supported by the European Commission (EU-INCO-DC contract number INCO-FP6u ˆ003740), as well as grants from the Research Council of Norway (NRC project no 151054 and 172226) and the Norwegian Council of Universities’ Committee for Development Research and Education (NUFU project number PRO 36/2002 and 2007/10177), and funding from the Danish Council of Developmental Research (91128). The sponsors of the study had no role in study design, collection, analysis and interpretation of data, or writing of the report. Address for correspondence: Tor A. Strand, PhD, Centre for International Health, University of Bergen, PO Box 7804, N-5020 Bergen, Norway. E-mail: tor.strand@cih.uib.no. Copyright © 2009 by Lippincott Williams & Wilkins ISSN: 0891-3668/10/2901-0001 DOI: 10.1097/INF.0b013e3181c2a1b9 The Pediatric Infectious Disease Journal • Volume 29, Number 1, January 2010 www.pidj.com | e1