Correspondence

Human Metapneumovirus and Lower Respiratory Tract Disease in Children

N Engl J Med 2004; 350:1788-1790April 22, 2004

Article

To the Editor:

The case definition of croup given by Williams et al. in their study of metapneumovirus (Jan. 29 issue)1 seems misleading. The authors state that croup is an “acute lower respiratory tract infection characterized by hoarseness, cough, and stridor.” On the contrary, croup is classified as an acute upper-airway disease in several textbooks of pediatrics.2-4 Recognizing croup as an important cause of acute upper-airway obstruction and its pertinent features, as distinct from life-threatening bacterial epiglottitis, is the classic point made in medical teaching worldwide.

Hok-Kung Ho, M.B., B.S.
University of Hong Kong, Hong Kong, China
a8914760@graduate.hku.hk

4 References

1. 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
   Full Text | Web of Science | Medline

2. 2

   Orenstein DM. Acute inflammatory upper airway obstruction. In: Behrman RE, Kliegman RM, Arvin AM, eds. Nelson textbook of pediatrics. 15th ed. Philadelphia: W.B. Saunders, 1996:1201-5.
   

3. 3

   Healy G, Avery ME. Upper airway disorders. In: Avery ME, First LR, eds. Pediatric medicine. 2nd ed. Baltimore: Williams & Wilkins, 1994:1347-56.
   

4. 4

   McKenzie S, Silverman M. Respiratory disorders. In: Campbell AGM, McIntosh N, eds. Forfar & Arneil's textbook of pediatrics. 5th ed. New York: Churchill Livingstone, 1998:489-583.
   

To the Editor:

Williams et al. show that “human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus.” In a surveillance study performed from November 1, 2002, to March 31, 2003, among 1331 healthy children younger than 15 years of age who were seen for acute respiratory infection in an emergency department in Milan, Italy, we found evidence of human metapneumovirus in 41 children (3.1 percent), of respiratory syncytial virus in 117 (8.8 percent, P<0.001 for the comparison with human metapneumovirus), and of influenzavirus in 209 (15.7 percent; P<0.001 for the comparison with human metapneumovirus) (Table 1Table 1Clinical Characteristics and Outcomes among Children Seen in the Emergency Department for Acute Respiratory Infection and Effects among Their Household Contacts, According to Viral RNA Detection.). Although the overall prevalence of human metapneumovirus in our study population appeared to be lower than the prevalence of respiratory syncytial virus and that of influenzavirus, we showed that this pathogen has multiple effects. We confirmed that infection with human metapneumovirus has clinical characteristics similar to those of infection with respiratory syncytial virus,1,2 but its socioeconomic effect appeared to be greater than that of respiratory syncytial virus infection and similar to that of influenzavirus infection.3,4 We would like to know whether the authors observed the same socioeconomic burden on children and their families in association with human metapneumovirus infection.

Nicola Principi, M.D.
Susanna Esposito, M.D.
Samantha Bosis, M.D.
Institute of Pediatrics, 20122 Milan, Italy
nicola.principi@unimi.it

4 References

1. 1

   Mejias A, Chavez-Bueno S, Ramilo O. Human metapneumovirus: a not so new virus. Pediatr Infect Dis J 2004;23:1-10
   Web of Science | Medline

2. 2

   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
   CrossRef | Web of Science | Medline

3. 3

   Principi N, Esposito S. Are we ready for universal influenza vaccination in paediatrics? Lancet Infect Dis 2004;4:75-83
   CrossRef | Web of Science | Medline

4. 4

   Principi N, Esposito S, Marchisio P, Gasparini R, Crovari P. Socioeconomic impact of influenza on healthy children and their families. Pediatr Infect Dis J 2003;22:Suppl:S207-S210
   Web of Science | Medline

Author/Editor Response

In response to Dr. Ho: we agree that the croup is usually poorly defined, partly because of differences between anatomical and physiological descriptions of this illness. Two standard textbooks of pediatrics define croup, or laryngotracheobronchitis, as both a cause of “upper airway obstruction” and “lower respiratory tract” infection.1,2 The classic pathophysiology involves subglottic tracheal edema (the “steeple sign” seen on radiographs of the airway). The World Health Organization defines lower respiratory tract infection as the presence of tachypnea, retractions, stridor, wheezing, or apnea.3 We think that recognition of croup as a distinct clinical syndrome is more valuable than a definition based on anatomical terms and define it as such in our article. There are an estimated 65,000 annual hospitalizations for croup in children less than five years old in the United States, thus warranting such a distinction and underscoring the importance of croup as a clinical entity.4

In response to the interesting data presented by Dr. Principi and colleagues: information about the age distribution of the patients they describe would help in the interpretation of the data. As we state in our article, all the children we studied were less than five years old and thus not in school. We did not collect data on parents' time off from work or other socioeconomic costs associated with illnesses due to human metapneumovirus infection. However, since the mean duration of symptoms before medical attention was sought was 4.4 days, and 37 percent of the children had concomitant acute otitis media, it is likely that there is a significant socioeconomic burden associated with disease caused by human metapneumovirus, as has been described for other respiratory viruses.4

Finally, we would like to clarify the financial support of our research. The work was supported by grants (T-32 AI07474 and R03 AI054790 [both to Dr. Williams] and R00095 [to the General Clinical Research Center]) from the National Institutes of Health and by a Vanderbilt University Discovery grant (to Dr. Crowe).

John V. Williams, M.D.
James E. Crowe, Jr., M.D.
Vanderbilt University, Nashville, TN 37232
james.crowe@vanderbilt.edu

4 References

1. 1

   Behrman RE, Kliegman RM, Arvin AM, eds. Nelson textbook of pediatrics. 15th ed. Philadelphia: W.B. Saunders, 1996.
   

2. 2

   Rudolph AM, ed. Rudolph's pediatrics. 20th ed. Stamford, Conn.: Appleton & Lange, 1996.
   

3. 3

   Emerging and communicable diseases: surveillance and control. Geneva: World Health Organization, 1997.
   

4. 4

   Henrickson KJ, Hoover S, Kehl KS, Hua W. National disease burden of respiratory viruses detected in children by polymerase chain reaction. Pediatr Infect Dis J 2004;23:Suppl:S11-S18
   CrossRef | Web of Science | Medline

Citing Articles (6)

Citing Articles

1. 1

   G. CILLA, E. OÑATE, E. G. PEREZ-YARZA, M. MONTES, D. VICENTE, E. PEREZ-TRALLERO. (2009) Hospitalization rates for human metapneumovirus infection among 0- to 3-year-olds in Gipuzkoa (Basque Country), Spain. Epidemiology and Infection 137:01, 66
   CrossRef

2. 2

   Susanna Esposito, Paola Marchisio, Nicola Principi. (2008) The Global State of Influenza in Children. The Pediatric Infectious Disease Journal 27:Supplement, S149-S153
   CrossRef

3. 3

   S. Bosis, S. Esposito, H. G. M. Niesters, G. V. Zuccotti, G. Marseglia, M. Lanari, G. Zuin, C. Pelucchi, A. D. M. E. Osterhaus, N. Principi. (2008) Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences. Clinical Microbiology and Infection 14:7, 677-684
   CrossRef

4. 4

   Susanna Esposito, Samantha Bosis, Hubert G.M. Niesters, Elena Tremolati, Enrica Begliatti, Alessandro Rognoni, Claudia Tagliabue, Nicola Principi, Albert D.M.E. Osterhaus. (2006) Impact of human coronavirus infections in otherwise healthy children who attended an emergency department. Journal of Medical Virology 78:12, 1609-1615
   CrossRef

5. 5

   N. Principi, S. Bosis, S. Esposito. (2006) Human metapneumovirus in paediatric patients. Clinical Microbiology and Infection 12:4, 301-308
   CrossRef

6. 6

   Oliver Schildgen, Arne Simon, Anja Wilkesmann, John Williams, Anna-Maria Eis-Hübinger, Bernd Kupfer, Michael Roggendorf, Sergei Viazov. (2006) The human metapneumovirus: biology, epidemiological features, and clinical characteristics of infection. Reviews in Medical Microbiology 17:1, 11-25
   CrossRef