Viral pneumonia

Olli Ruuskanen, Elina Lahti, Lance C Jennings, David R Murdoch, Olli Ruuskanen, Elina Lahti, Lance C Jennings, David R Murdoch

Abstract

About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Age-specific incidence of community-acquired pneumonia Error bars=95% CIs. Modified from reference with permission of Oxford University Press.
Figure 2
Figure 2
Chest radiographs of patients with viral pneumonia (A) Pneumonia caused by human bocavirus in a 1-year-old girl. Chest radiograph shows alveolar infiltrates in right middle lobe and left lower lobe. (B) Pneumonia caused by metapneumovirus and Haemophilus influenzae in a 7-year-old girl. Chest radiograph shows alveolar infiltrate in left lower lobe. (C) Pneumonia caused by rhinovirus and Streptococcus pneumoniae in an 11-year-old girl. Chest radiograph shows alveolar infiltrate in right lower lobe. (D) Pneumonia caused by adenovirus in a 22-year-old man. Chest radiograph shows alveolar and interstitial infiltrates in right lower lobe.
Figure 3
Figure 3
Immunolocalisation of 2009 pandemic influenza H1N1 viral antigen in lung tissue Viral antigens (red staining) are present in nuclei of alveolar-lining cells. Reprinted from reference with permission of the American Society for Investigative Pathology.

References

    1. British Thoracic Society of Standards of Care Committee BTS guidelines for the management of community acquired pneumonia in childhood. Thorax. 2002;57(suppl 1):i1–24.
    1. McIntosh K. Community-acquired pneumonia in children. N Engl J Med. 2002;346:429–437.
    1. File TM. Community-acquired pneumonia. Lancet. 2003;362:1991–2001.
    1. Durrington HJ, Summers C. Recent changes in the management of community-acquired pneumonia in adults. BMJ. 2008;336:1429–1433.
    1. Lim WS, Baudoin SV, George RC, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(suppl III):iii1–ii55.
    1. Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ. 2008;86:408–416.
    1. WHO Revised global burden of disease 2002 estimates. 2004. (accessed Nov 5, 2010).
    1. Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol. 1993;137:977–988.
    1. Black RE, Cousens S, Johnson HL, et al. for the Child Health Epidemiology Reference Group of WHO and UNICEF Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:1969–1987.
    1. de Wals P, Robin E, Fortin E, Thibeault R, Ouakki M, Douville-Fradet M. Pneumonia after implementation of the pneumococcal conjugate vaccine program in the province of Quebec, Canada. Pediatr Infect Dis J. 2008;27:963–968.
    1. Simpson JCG, Macfarlane JT, Watson J, Woodhead MA. A national confidential enquiry into community acquired pneumonia deaths in young adults in England and Wales. Thorax. 2000;55:1040–1045.
    1. File TM, Marrie TJ. Burden of community acquired pneumonia in North American adults. Postgrad Med. 2010;122:130–141.
    1. Murdoch DR, O'Brien KL, Scott AG, et al. Breathing new life into pneumonia diagnostics. J Clin Microbiol. 2009;47:3405–3408.
    1. Lieberman D, Lieberman D, Shimoni A, Keren-Naus A, Steinberg R, Shemer-Avni Y. Identification of respiratory viruses in adults: nasopharyngeal versus oropharyngeal sampling. J Clin Microbiol. 2009;47:3439–3443.
    1. Loens K, Van Heirstraeten L, Malhotra-Kumar S, Goossens H, Ieven M. Optimal sampling sites and methods for detection of pathogens possibly causing community-acquired lower respiratory tract infections. J Clin Microbiol. 2009;47:21–31.
    1. Ruohola A, Waris M, Allander T, Ziegler T, Heikkinen T, Ruuskanen O. Viral etiology of common cold in children, Finland. Emerg Infect Dis. 2009;15:344–346.
    1. Heikkinen T, Marttila J, Salmi AA, Ruuskanen O. Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses. J Clin Microbiol. 2002;40:4337–4339.
    1. Peltola V, Waris M, Österback R, Susi P, Ruuskanen O, Hyypiä T. Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections. J Infect Dis. 2008;197:382–389.
    1. Jennings LC, Anderson TP, Beynon KA, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008;63:42–48.
    1. Johansson N, Kalin M, Tiveljung-Lindell A, Giske C, Hedlund J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis. 2010;50:202–209.
    1. Lahti E, Peltola V, Waris M, et al. Induced sputum in the diagnosis of childhood community-acquired pneumonia. Thorax. 2009;64:252–257.
    1. Adegbola RA, Falade AG, Sam BE, et al. The etiology of pneumonia in malnourished and well-nourished Gambian children. Pediatr Infect Dis J. 1994;13:975–982.
    1. Vuori-Holopainen E, Peltola H. Reappraisal of lung tap: review of an old methods for better etiologic diagnosis of childhood pneumonia. Clin Infect Dis. 2001;32:715–726.
    1. Talbot HK, Falsey AR. The diagnosis of viral respiratory disease in older adults. Clin Infect Dis. 2010;50:747–751.
    1. She RC, Polage CR, Caram LB, et al. Performance of diagnostic tests to detect respiratory viruses in older adults. Diagn Microbiol Infect Dis. 2010;67:246–250.
    1. Tiveljung-Lindell A, Rotzen-Östlund M, Gupta S, et al. Development and implementation of a molecular diagnostic platform for daily rapid detection of 15 respiratory viruses. J Med Virol. 2009;81:167–175.
    1. Arens MQ, Buller RS, Rankin A, et al. Comparison of the Eragen multi-code respiratory virus panel with conventional viral testing and real-time multiplex PCR assays for detection of respiratory viruses. J Clin Microbiol. 2010;48:2387–2395.
    1. Murdoch DR, Jennings LC, Bhat N, Anderson TP. Emerging advances in rapid diagnostics of respiratory infections. Infect Dis Clin North Am. 2010;24:791–807.
    1. Mäkelä MJ, Puhakka T, Ruuskanen O, et al. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. 1998;36:539–542.
    1. Juvén T, Mertsola J, Waris M, et al. Etiology of community-acquired pneumonia in 254 hospitalized children. Pediatr Infect Dis J. 2000;19:293–298.
    1. van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. 2009;374:1543–1556.
    1. Flood R, Badik J, Aronoff S. The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children. Pediatr Infect Dis J. 2008;27:95–99.
    1. Virkki R, Juven T, Rikalainen H, Svedström E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax. 2002;57:438–441.
    1. Schuetz P, Albrich W, Christ-Crain M, Chastre J, Mueller B. Procalcitonin for guidance of antibiotic therapy. Expert Rev Anti Infect Ther. 2010;8:575–587.
    1. Gilbert DN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol. 2010;48:2325–2329.
    1. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27–S72.
    1. Toikka P, Virkki R, Mertsola J, Ashorn P, Eskola J, Ruuskanen O. Bacteremic pneumococcal pneumonia in children. Clin Infect Dis. 1999;29:568–572.
    1. Shiley KT, van Deerlin VM, Miller WT., Jr Chest CT features of community-acquired respiratory viral infections in adult inpatients with lower respiratory tract infections. J Thorac Imaging. 2010;25:68–75.
    1. Juvén T, Mertsola J, Waris M, Leinonen M, Ruuskanen O. Clinical response to antibiotic therapy for community-acquired pneumonia. Eur J Pediatr. 2004;163:140–144.
    1. Tsolia MN, Psarras S, Bossios A, et al. Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections. Clin Infect Dis. 2004;39:681–686.
    1. Cilla G, Oñate E, Perez-Yarza EG, Montes M, Vicente D, Perez-Trallero E. Viruses in community-acquired pneumonia in children aged less than 3 years old: high rate of viral coinfection. J Med Virol. 2008;80:1843–1849.
    1. Hamano-Hasegawa K, Morozumi M, Nakayama E, et al. Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia. J Infect Chemother. 2008;14:424–432.
    1. Nascimento-Carvalho CM, Ribeiro CT, Cardoso MRA, et al. The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country. Pediatr Infect Dis J. 2008;27:939–941.
    1. Samramsamruajkit R, Hiranrat T, Chieochansin T, et al. Prevalence, clinical presentations and complications among hospitalized children with influenza pneumonia. Jpn J Infect Dis. 2008;6:446–449.
    1. Cevey-Macherel M, Galetto-Lacour A, Gervaix A, et al. Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines. Eur J Pediatr. 2009;168:1429–1436.
    1. Wolf DG, Greenberg D, Shemer-Avni Y, Givon-Lavi N, Bar-Ziv J, Dagan R. Association of human metapneumovirus with radiologically diagnosed community-acquired alveolar pneumonia in young children. J Pediatr. 2010;156:115–120.
    1. Ausina V, Coll P, Sambeat M, et al. Prospective study on the etiology of community-acquired pneumonia in children and adults in Spain. Eur J Clin Microbiol Infect Dis. 1988;7:343–347.
    1. Claesson BA, Trollfors B, Brolin I, et al. Etiology of community-acquired pneumonia in children based on antibody responses to bacterial and viral antigens. Pediatr Infect Dis J. 1989;8:856–862.
    1. Heiskanen-Kosma T, Korppi M, Jokinen C, et al. Etiology of chilhood pneumonia: serologic results of a prospective, population-based study. Pediatr Infect Dis J. 1998;17:986–991.
    1. Don M, Fasoli L, Paldanius M, et al. Aetiology of community-acquired pneumonia: serological results of a paediatric survey. Scand J Infect Dis. 2005;37:806–812.
    1. Peltola V, Jartti T, Putto-Laurila A, et al. Rhinovirus infections in children: a retrospective and prospective hospital-based study. J Med Virol. 2009;81:1831–1838.
    1. Berkley JA, Munywoki P, Ngama M, et al. Viral etiology of severe pneumonia among Kenyan children and infants. JAMA. 2010;303:2051–2057.
    1. Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–1555.
    1. Hayden FG. Rhinovirus and the lower respiratory tract. Rev Med Virol. 2004;14:17–31.
    1. Calvo C, García-García ML, Blanco C, Pozo F, Flecha IC, Pérez-Breña P. Role of rhinovirus in hospitalized infants with respiratory tract infections in Spain. Pediatr Infect Dis J. 2007;26:904–908.
    1. Cheuk DKL, Tang IWH, Chan KH, Woo PCY, Peiris MJS, Chiu SS. Rhinovirus infection in hospitalized children in Hong Kong: a prospective study. Pediatr Infect Dis J. 2007;26:995–1000.
    1. Miller EK, Edwards KM, Weinberg GA, et al. A novel group of rhinoviruses is associated with asthma hospitalizations. J Allergy Clin Immunol. 2009;123:98–104.
    1. Miller EK, Lu X, Erdman DD, et al. for the New Vaccine Surveillance Network Rhinovirus-associated hospitalizations in young children. J Infect Dis. 2007;195:773–781.
    1. Pierangeli A, Gentile M, Di Marco P, et al. Detection and typing by molecular techniques of respiratory viruses in children hospitalized for acute respiratory infection in Rome, Italy. J Med Virol. 2007;79:463–468.
    1. Renwick N, Schweiger B, Kapoor V, et al. A recently identified rhinovirus genotype is associated with severe respiratory tract infection in children in Germany. J Infect Dis. 2007;196:1754–1760.
    1. Louie JK, Roy-Burman A, Guardia-LaBar L, et al. Rhinovirus associated with severe lower respiratory tract infections in children. Pediatr Infect Dis J. 2009;28:337–339.
    1. Jartti T, Jartti L, Peltola V, Waris M, Ruuskanen O. Identification of respiratory viruses in asymptomatic subjects: asymptomatic respiratory viral infections. Pediatr Infect Dis J. 2008;27:1103–1107.
    1. Werno AM, Anderson TP, Jennings LC, Jackson PM, Murdoch DR. Human metapneumovirus in children with bronchiolitis or pneumonia. J Paediatr Child Health. 2004;40:549–551.
    1. Esper F, Boucher D, Weibel C, Martinello RA, Kahn JS. Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics. 2003;111:1407–1410.
    1. Williams JV, Harris PA, Tollefson SJ, et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004;350:443–450.
    1. Camps M, Ricart S, Dimova V, et al. Prevalence of human metapneumovirus among hospitalized children younger than 1 year in Catalonia, Spain. J Med Virol. 2008;80:1452–1460.
    1. Schildgen O, Muller A, Allander T, et al. Human bocavirus: passenger or pathogen in acute respiratory tract infections? Clin Microbiol Rev. 2008;21:291–304.
    1. Fry AM, Lu X, Chittaganpitch M, et al. Human bocavirus: a novel parvovirus epidemiologically associated with pneumonia requiring hospitalization in Thailand. J Infect Dis. 2007;195:1038–1045.
    1. Söderlund-Venermo M, Lahtinen A, Jartti T, et al. Clinical assessment and improved diagnosis of bocavirus-induced wheezing in children, Finland. Emerg Infect Dis. 2009;15:1423–1430.
    1. Don M, Söderlund-Venermo M, Valent F, et al. Serologically verified human bocavirus pneumonia in children. Pediatr Pulmonol. 2010;45:120–126.
    1. Carballal G, Videla C, Misirlian A, Requeijo PV, Aguilar MC. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children. BMC Pediatr. 2002;2:6.
    1. Ou Z-Y, Zeng Q-Y, Wang F-H, et al. Retrospective study of adenovirus in autopsied pulmonary tissue of pediatric fatal pneumonia in South China. BMC Infect Dis. 2008;8:122.
    1. Arnold JC, Singh KK, Spector SA, Sawyer MH. Undiagnosed respiratory viruses in children. Pediatrics. 2008;121:e631–e637.
    1. Heugel J, Martin ET, Kuypers J, Englund JA. Coronavirus-associated pneumonia in previously healthy children. Pediatr Infect Dis J. 2007;26:753–755.
    1. Lau SKP, Woo PCY, Yip CCY, et al. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J Clin Microbiol. 2006;44:2063–2071.
    1. Dare RK, Fry AM, Chittaganpitch M, Sawanpanyalert P, Olsen SJ, Erdman DD. Human coronavirus infections in rural Thailand: a comprehensive study using real-time reverse-transcription polymerase chain reaction assays. J Infect Dis. 2007;96:1321–1328.
    1. Templeton KE, Scheltinga SA, van den Eeden WCJFM, Graffelman AW, van den Broek PJ, Claas ECJ. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis. 2005;41:345–351.
    1. Marcos MA, Camps M, Pumarola T, et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther. 2006;11:351–359.
    1. Saito A, Kohno S, Matsushima T, et al. Prospective multicenter study of the causative organisms of community-acquired pneumonia in adults in Japan. J Infect Chemother. 2006;12:63–69.
    1. Charles PG, Whirby M, Fuller AJ, et al. The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin Infect Dis. 2008;46:1513–1521.
    1. Hohenthal U, Vainionpää R, Meurman O, et al. Aetiological diagnosis of community acquired pneumonia: utility of rapid microbiological methods with respect to disease severity. Scand J Infect Dis. 2008;40:131–138.
    1. Hohenthal U, Vainionpää R, Nikoskelainen J, Kotilainen P. The role of rhinovirus and enteroviruses in community acquired pneumonia in adults. Thorax. 2008;63:658–659.
    1. Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134:1141–1148.
    1. Diederen BMW, Van Der Eerden MM, Vlaspolder F, Boersma WG, Kluytmans JAJW, Peeters MF. Detection of respiratory viruses and Legionella spp by real-time polymerase chain reaction in patients with community acquired pneumonia. Scand J Infect Dis. 2009;41:45–50.
    1. Lieberman D, Shimoni A, Shemer-Avni Y, Keren-Naos A, Shtainberg R, Lieberman D. Respiratory viruses in adults with community-acquired pneumonia. Chest. 2010;138:811–816.
    1. Ruiz M, Ewig S, Marcos MA, et al. Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity. Am J Respir Crit Care Med. 1999;160:397–405.
    1. Lim WS, Macfarlane JT, Boswell TCJ, et al. Study of community acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management. Thorax. 2001;56:296–301.
    1. Lauderdale T, Chang F, Ben R, et al. Etiology of community acquired pneumonia among adults patients requiring hospitalization in Taiwan. Respir Med. 2005;99:1079–1086.
    1. Almirall J, Boixeda R, Bolibar I, et al. Differences in the etiology of community-acquired pneumonia according to site of care: a population-based study. Respir Med. 2007;101:2168–2175.
    1. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–1759.
    1. Han LL, Alexander JP, Anderson LJ. Respiratory syncytial virus pneumonia among the elderly: an assessment of disease burden. J Infect Dis. 1999;179:25–30.
    1. Thompson WW, Shay DK, Weistraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–186.
    1. Hicks LA, Shepard CW, Britz PH, et al. Two outbreaks of severe respiratory disease in nursing homes associated with rhinovirus. J Am Geriatr Soc. 2006;54:284–289.
    1. Longtin J, Marchand-Austin A, Winter A, et al. Rhinovirus outbreaks in long-term care facilities, Ontario, Canada. Emerg Infect Dis. 2010;16:1463–1465.
    1. Tucker SN, Tingley DW, Scallan CD. Oral adenoviral-based vaccines: historical perspective and future opportunity. Expert Rev Vaccines. 2008;7:25–31.
    1. Esposito DH, Gardner TJ, Schneider E, et al. Outbreak of pneumonia associated with emergent human adenovirus serotype 14: southeast Alaska, 2008. Clin Infect Dis. 2010;202:214–222.
    1. Woo PCY, Lau SKP, Tsoi H-W, et al. Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia. J Infect Dis. 2005;192:1898–1907.
    1. Boivin G, De Serres G, Hamelin M-E, et al. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long term-care facility. Clin Infect Dis. 2007;44:1152–1158.
    1. Louie JK, Schnurr DP, Pan C-Y, et al. A summer outbreak of human metapneumovirus infection in a long-term-care facility. J Infect Dis. 2007;196:705–708.
    1. Walsh EE, Peterson DR, Falsey AR. Human metapneumovirus infections in adults: another piece of the puzzle. Arch Intern Med. 2008;168:2489–2496.
    1. Levy MM, Baylor MS, Bernard GR, et al. Clinical issues and research in respiratory failure from severe acute respiratory syndrome. Am J Respir Crit Care Med. 2005;171:518–526.
    1. The Writing Committee of the World Health Organization (WHO) Consultation on human influenza A/H5 Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005;353:1374–1385.
    1. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010;362:1708–1719.
    1. Bishop JF, Murnane MP, Owen R. Australia's winter with the 2009 pandemic influenza A (H1N1) virus. N Engl J Med. 2009;361:2591–2594.
    1. Kotsimbos T, Waterer G, Jenkins C, et al. on behalf of the Thoracic Society of Australia and New Zealand H1N1 Influenza 09 Task Force Influenza A/H1N1_09: Australia and New Zealand's winter of discontent. Am J Respir Crit Care Med. 2010;181:300–306.
    1. Louie JK, Acosta M, Winter K, et al. for the California Pandemic (H1N1) Working Group Factors associated with death or hospitalization due to pandemic 2009 influenza A (H1N1) infection in California. JAMA. 2009;302:1896–1902.
    1. Poggensee G, Gilsdorf A, Buda S, et al. The first wave of pandemic influenza (H1N1) 2009 in Germany: from initiation to acceleration. BMC Infect Dis. 2010;10:155.
    1. Nguyen-Van-Tam JS, Openshaw PJM, Hashim A, et al. Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (May–September 2009) Thorax. 2010;65:645–651.
    1. Agarwal PP, Cinti S, Kazerooni EA. Chest radiographic and CT findings in novel swine-origin influenza A (H1N1) virus (S-OIV) infections. Am J Radiol. 2009;193:1488–1493.
    1. Drews AL, Atmar RL, Glezen WP, Baxter BD, Piedra PA, Greenberg SB. Dual respiratory virus infections. Clin Infect Dis. 1997;25:1421–1429.
    1. Jennings LC, Anderson TP, Werno AM, Beynon KA, Murdoch DR. Viral etiology of acute respiratory tract infections in children presenting to hospital: role of polymerase chain reaction and demonstration of multiple infections. Pediatr Infect Dis J. 2004;23:1003–1007.
    1. Calvo C, García-García ML, Blanco C, et al. Multiple simultaneous viral infections in infants with acute respiratory tract infections in Spain. J Clin Virol. 2008;42:268–272.
    1. Midulla F, Scagnolori C, Bonci E, et al. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child. 2010;95:35–41.
    1. Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis. 2008;198:962–970.
    1. Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A (H1N1) infection in Canada. JAMA. 2009;302:1872–1879.
    1. Forgie IM, O'Neill KP, Lloyd-Evans N, et al. Etiology of acute lower respiratory tract infections in Gambian children: II—acute lower respiratory tract infections in children ages one to nine years presenting at the hospital. Pediatr Infect Dis J. 1991;10:42–47.
    1. Johnson A-W, Osinusi K, Aderele WI, et al. Etiologic agents and outcome determinants of community-acquired pneumonia in urban children: a hospital-based study. J Nat Med Assoc. 2008;100:370–385.
    1. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev. 2006;19:571–582.
    1. Finelli L, Fiore A, Dhara R, et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics. 2008;122:805–811.
    1. Reed C, Kallen AJ, Patton M, et al. Infection with community-onset Staphylococcus aureus and influenza virus in hospitalized children. Pediatr Infect Dis J. 2009;28:572–576.
    1. Seki M, Kosai K, Yanagihara K, et al. Disease severity in patients with simultaneous influenza and bacterial pneumonia. Intern Med. 2007;46:953–958.
    1. Palacios G, Hornig M, Cisterna D, et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PloS One. 2009;4:e8540–e8544.
    1. do Carmo Debur M, Raboni SM, Flizikowski FBZ, et al. Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal and non-pandemic seasonal respiratory infections. J Clin Pathol. 2010;63:930–934.
    1. Bustamante-Calvillo ME, Velázquez FR, Cabrera-Munõz L, et al. Molecular detection of respiratory syncytial virus in postmortem lung tissue samples from Mexican children deceased with pneumonia. Pediatr Infect Dis J. 2001;20:495–501.
    1. Imakita M, Shiraki K, Yutani C, Ishibashi-Ueda H. Pneumonia caused by rhinovirus. Clin Infect Dis. 2000;30:611–612.
    1. Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod Pathol. 2007;20:108–119.
    1. Donoso AF, León JA, Camacho JF, Cruces PI, Ferrés M. Fatal hemorrhagic pneumonia caused by human metapneumovirus in an immunocompetent child. Pediatr Intern. 2008;50:589–591.
    1. Nicholls JM, Poon LLM, Lee KC, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003;361:1773–1778.
    1. Korteweg C, Jiang G. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans. Am J Pathol. 2008;172:1155–1170.
    1. Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, et al. Pathological changes associated with the 2009 H1N1 virus. N Engl J Med. 2009;361:2001–2003.
    1. Mauad T, Hajjar LA, Callegari GD, et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med. 2010;181:72–79.
    1. Shieh W-J, Blau DM, Denison AM, et al. 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol. 2010;177:166–175.
    1. Friis B, Andersen P, Brenoe E, et al. Antibiotic treatment of pneumonia and bronchiolitis. Arch Dis Child. 1984;59:1038–1045.
    1. Wong SSY, Yuen K-Y. Antiviral therapy for respiratory tract infections. Respirology. 2008;13:950–971.
    1. Shun-Shin M, Thompson M, Heneghan C, Perera R, Harnden A, Mant D. Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. BMJ. 2009;339:3172–3180.
    1. Yu H, Liao Q, Yuan Y, et al. Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China. BMJ. 2010;341:c4779.
    1. Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management—clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1003–1032.
    1. Birnkrant D, Cox E. The emergency use authorization of peramivir for treatment of 2009 H1N1 influenza. N Engl J Med. 2009;361:2204–2207.
    1. Härter G, Zimmermann O, Maier L, et al. Intravenous zanamivir for patients with pneumonitis due to pandemic (H1N1) 2009 influenza virus. Clin Infect Dis. 2010;50:1249–1251.
    1. Yin MT, Brust JCM, van Tieu H, Hammer SM. In: Clinical virology. 3rd edn. Richman DD, Whitley RJ, Hayden FG, editors. ASM Press; Washington: 2009. Antiherpes, anti-hepatitis virus, and anti-respiratory virus agents; pp. 217–264.
    1. Hopkins P, McNeil K, Kermeen F, et al. Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus. Am J Respir Crit Care Med. 2008;178:876–881.
    1. Empey KM, Pebbles S, Koll JK. Pharmacologic advances in the treatment and prevention of respiratory syncytial virus. Clin Infect Dis. 2010;50:1258–1267.
    1. Doan ML, Mallory GB, Kaplan SL, et al. Treatment of adenovirus pneumonia with cidofovir in pediatric lung transplant recipients. J Heart Lung Transplant. 2007;26:883–889.
    1. Bonney D, Razali H, Turner A, Will A. Successful treatment of human metapneumovirus pneumonia using combination therapy with intravenous ribavirin and immune globulin. Br J Haematol. 2009;145:667–669.
    1. Frangites CY, Pneumatikos I. Varicella-zoster virus pneumonia in adults: report of 14 cases and review of the literature. Eur J Intern Med. 2004;15:364–370.
    1. Jartti T, Vanto T, Heikkinen T, Ruuskanen O. Systemic glucocorticoids in childhood expiratory wheezing: relation between age and viral etiology with efficacy. Pediatr Infect Dis J. 2002;21:873–878.
    1. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3:e343.
    1. Falagas ME, Vouloumanou EK, Baskouta E, Rafailidis PI, Polyzos K, Rello J. Treatment options for 2009 H1N1 influenza: evaluation of the published evidence. Int J Antimicrob Agents. 2010;35:421–430.
    1. Cheng VCC, Tang BSF, Wu AKL, Chu CM, Yuen KY. Medical treatment of viral pneumonia including SARS in immunocompetent adult. J Infect. 2004;49:262–273.
    1. Heinonen S, Silvennoinen H, Lehtinen P, Vainionpää R, Ziegler T, Heikkinen T. Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study. Lancet Infect Dis (published online Nov 23, 2010). DOI:10.1016/S1473-3099(10)70255-3.
    1. American Academy of Pediatrics Policy statement: modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124:1694–1701.
    1. Madhi SA, Klugman KP, The Vaccine Trialist Group A role for Streptococcus pneumoniae in virus associated pneumonia. Nat Med. 2004;10:811–813.

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