PEDIATRICS Vol. 121 No. 2 February 2008, pp. 446-447 (doi:10.1542/peds.2007-3386)
LETTER TO THE EDITOR |
Human Metapneumovirus and Human Coronavirus NL63: In Reply
Stephen B. Lambert, MBBSKelly M. Allen, MPH
Vaccine and Immunisation Research Group
University of Melbourne and the Murdoch Children's Research Institute
Melbourne, Victoria, Australia 3010
Theo P. Sloots, PhD
Michael D. Nissen, FRACP
Queensland Paediatric Infectious Diseases Laboratory
Royal Children's Hospital
Brisbane, Queensland, Australia 4029
Terry M. Nolan, PhD
Vaccine and Immunisation Research Group
University of Melbourne and the Murdoch Children's Research Institute
Melbourne, Victoria, Australia 3010
In Reply.—
We thank Pilger and Cantarelli for their comments on our article. We agree that, as with all observational studies, ours had potential bias issues that may limit interpretability. The job for readers is to assess to what extent such biases invalidate the reported results.
The reference used to highlight potential issues with different specimen types was a study conducted on a variety of specimens from a relatively narrow population: children hospitalized with severe acute lower respiratory tract disease.1 In our opinion, there is a lack of data in the published literature on the broad range of community-managed acute respiratory illnesses (ARIs). For this reason, one of the aims of our study was to assess the utility of the relatively noninvasive, parent-collected nose-throat swabs. Bronchoalveolar lavage and tracheal secretions are too invasive and not suitable for a study that examines mostly upper respiratory tract disease. We feel that in community-based studies, even less invasive tests may introduce more bias (because of underreporting of ARI episodes) than they prevent if they require a disruptive home visit for collection. Any underestimation of virus-specific rates caused by using nose-throat swabs is likely to be small; the proportion of ARIs in our study that tested positive for any virus (74%)2 fell within the range of recent home-visit studies that used polymerase chain reaction (PCR) for diagnosis and nasopharyngeal aspirates (69%)3 or nasal lavage (83%).4
ARIs that require specimen collection and impact diary completion were identified in our study by parents using a simple and sensitive symptom-based algorithm.2 This method has been used in a phase III influenza vaccine-efficacy study5 and by us in a pilot study.6,7 Parents were not required to classify symptom severity but, rather, were asked to merely identify daily presence or absence. In a poststudy questionnaire (response rate: 78%), parents in our study were asked to nominate the most difficult study procedure: keeping the daily symptom diary was nominated by only 11% of respondents.
We agree that real-time PCR, used to identify human metapneumovirus and human coronavirus NL63 in our study, is likely to be more sensitive that the conventional PCR method used to identify other viruses, but false-positive results are likely to be uncommon with either method.8 Therefore, the use of real-time PCR is unlikely to overestimate the presence of human metapneumovirus and human coronavirus NL63, but conventional PCR may lead to an underestimation of the role of the other viruses.
REFERENCES
1. Kleines M, Scheithauer S, Rackowitz A, Ritter K, Häusler M. High prevalence of human bocavirus detected in young children with severe acute lower respiratory tract disease by use of a standard PCR protocol and a novel real-time PCR protocol.
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2. Lambert SB, Allen KM, Druce JD, et al. Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool-aged children using parent-collected specimens. Pediatrics. 2007;120 (4). Available at: www.pediatrics.org/cgi/content/full/120/4/e929
3. Kusel MM, de Klerk NH, Holt PG, Kebadze T, Johnston SL, Sly PD. Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study. Pediatr Infect Dis J. 2006;25 (8):680 –686[CrossRef][Web of Science][Medline]
4. Legg JP, Warner JA, Johnston SL, Warner JO. Frequency of detection of picornaviruses and seven other respiratory pathogens in infants. Pediatr Infect Dis J. 2005;24 (7):611 –616[CrossRef][Web of Science][Medline]
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6. Lambert S, O'Grady KA, Gabriel S, Carter R, Nolan T. The cost of seasonal respiratory illnesses in Australian children: the dominance of patient and family costs and implications for vaccine use. Commun Dis Intell. 2004;28 :510 –516[Medline]
7. Lambert SB, O'Grady KF, Gabriel SH, Nolan TM. Respiratory illness during winter: a cohort study of urban children from temperate Australia. J Paediatr Child Health. 2005;41 (3):125 –129[CrossRef][Web of Science][Medline]
8. Ratcliff RM, Chang G, Kok T, Sloots TP. Molecular diagnosis of medical viruses. Curr Issues Mol Biol. 2007;9 (2):87 –102[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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