Correspondence

Respiratory Viruses and Acute Otitis Media

N Engl J Med 1999; 340:2001-2002June 24, 1999

Article

To the Editor:

Heikkinen et al. (Jan. 28 issue)1 studied the prevalence of various respiratory viruses in samples of middle-ear effusions from children with acute otitis media and found that respiratory syncytial virus had the highest rate of detection. Although respiratory viruses may differ in their capacity to invade the middle ear, any comparison of the frequencies of and differences in infection depends heavily on the sensitivity of the methods used to determine the presence of viral infection. The methods used by Heikkinen et al. were not optimal for detecting certain respiratory viruses, particularly human rhinoviruses and coronaviruses.

In a recent study in which we used a reverse-transcription–polymerase-chain-reaction (RT-PCR) assay to detect viral RNA in nasal aspirates and middle-ear effusions from children with acute otitis media, we found evidence of infection by human rhinovirus in 35 percent of the children, respiratory syncytial virus in 28 percent, and human coronavirus in 17 percent.2 Overall, viral RNA was detected in 75 percent of the children and in 48 percent of samples of middle-ear effusions at the time of the diagnosis of acute otitis media. Among the infected children, human rhinovirus RNA was found in 64 percent of middle-ear effusions, respiratory syncytial virus in 57 percent, and human coronavirus in 36 percent.2 Thus, we found that human rhinovirus was implicated in acute otitis media and detectable in middle ear effusions at least as frequently as respiratory syncytial virus. Detection of human rhinovirus by culture and RT-PCR in samples of middle-ear effusions from children with otitis media also indicates the invasive potential of human rhinovirus in otitis media.3 . . .

Anne Pitkäranta, M.D.
University of Helsinki, 00290 Helsinki, Finland

Frederick G. Hayden, M.D.
University of Virginia, Charlottesville, VA 22908

3 References

1
Heikkinen T, Thint M, Chonmaitree T. Prevalence of various respiratory viruses in the middle ear during acute otitis media. N Engl J Med 1999;340:260-264
Full Text | Web of Science | Medline

2
Pitkaranta A, Virolainen A, Jero J, Arruda E, Hayden FG. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 1998;102:291-295
CrossRef | Web of Science | Medline

3
Pitkaranta A, Jero J, Arruda E, Virolainen A, Hayden FG. Polymer-ase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion. J Pediatr 1998;133:390-394
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To the Editor:

Focusing on the role of viruses in the cause and pathogenesis of acute otitis media is very important. We agree with Heikkinen et al. and with Eskola and Hovi, who wrote the accompanying editorial,1 that preventing these viral infections may have an effect on the incidence of acute otitis media. Unfortunately, until now, the evidence that vaccinations are effective in preventing acute otitis media has not been convincing. There have been three studies of viral vaccinations to prevent acute otitis media.2-4 The earlier study by Heikkinen et al.2 was neither double-blinded nor placebo-controlled. The study by Clements et al.3 showed a reduction of acute otitis media in the vaccinated group only during the six weeks of an influenza epidemic. The study by Belshe et al.4 involved only cases of febrile acute otitis media, which account for only about half of all cases.

Moreover, for vaccination to be effective, we would have to vaccinate many children against many viruses. Respiratory syncytial virus and influenzaviruses accounted for only 19.5 percent of the episodes of acute otitis media in the study by Heikkinen et al. The effectiveness of pneumococcal vaccinations in preventing acute otitis media has not been promising, either. Perhaps the results with the conjugated vaccine will be better. In view of these facts, it is doubtful that vaccination to prevent acute otitis media will be cost effective. . . .

Roger A.M.J. Damoiseaux, M.D.
Frank A.M. van Balen, M.D., Ph.D.
Theo J.M. Verheij, M.D., Ph.D.
Utrecht University, 3584 CG Utrecht, the Netherlands

4 References

1
Eskola J, Hovi T. Respiratory viruses in acute otitis media. N Engl J Med 1999;340:312-314
Full Text | Web of Science | Medline

2
Heikkinen T, Ruuskanen O, Waris M, Ziegler T, Arola M, Halonen P. Influenza vaccination in the prevention of acute otitis media in children. Am J Dis Child 1991;145:445-448
Web of Science | Medline

3
Clements DA, Langdon L, Bland C, Walter E. Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. Arch Pediatr Adolesc Med 1995;149:1113-1117
Web of Science | Medline

4
Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med 1998;338:1405-1412
Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: It is well established that viral infection plays a key part in initiating the cascade of events that leads to the development of acute otitis media.1-3 Therefore, it is logical to hypothesize that prevention of the viral infection will also lead to prevention of acute otitis media. Unlike Damoiseaux et al., we believe that the data from the three randomized, controlled trials of influenza vaccine provide sufficient evidence to prove the hypothesis. Obviously, the efficacy of viral vaccines is virus-specific; the influenza vaccine cannot be expected to prevent any episodes of acute otitis media that follow infections by other viruses. The purpose of our study was to identify those viruses for which preventive measures, if available, might prove most beneficial in regard to acute otitis media. Influenza vaccine is currently the only available vaccine against respiratory viruses. The potential efficacy of other viral vaccines and the cost effectiveness of this approach in preventing acute otitis media remain to be determined.

We agree with Drs. Pitkäranta and Hayden that a comparison of the relative frequencies of viruses in the middle ear may depend on the sensitivity of the diagnostic methods used. The available diagnostic methods, including RT-PCR, may underdetect viral infection. Although RT-PCR assays are more sensitive than conventional viral studies, the limited volume of samples of middle-ear fluid and the high costs of such assays do not allow them to be performed for a wide range of respiratory viruses. Whatever method is used, the crucial issue in regard to the invasiveness of viruses is that similar methods should be used to detect viruses in the nasopharynx and in the middle ear.

With respect to rhinoviruses, we used cell lines and incubation temperatures that are considered appropriate for the detection of these viruses.4 The small number of rhinovirus infections that were diagnosed in the children in our study prevented any conclusions about the relative importance of rhinoviruses. We referred to the study by Pitkäranta et al.5 in our article, including their suggestion that the prevalence of rhinoviruses in middle-ear fluid during acute otitis media may be similar to the prevalence of respiratory syncytial virus. Their findings were based on studies of only 32 children with rhinovirus infection and 26 children with respiratory syncytial virus infection, so further studies are needed to determine the relative importance of rhinoviruses and other respiratory viruses.

Terho Heikkinen, M.D.
Turku University Hospital, FIN-20520 Turku, Finland

Tasnee Chonmaitree, M.D.
Monica Thint, M.D.
University of Texas Medical Branch, Galveston, TX 77555

5 References

1
Bluestone CD, Klein JO. Otitis media in infants and children. 2nd ed. Philadelphia: W.B. Saunders, 1995.

2
Chonmaitree T, Heikkinen T. Role of viruses in middle-ear disease. Ann N Y Acad Sci 1997;830:143-157
CrossRef | Web of Science | Medline

3
Arola M, Ruuskanen O, Ziegler T, et al. Clinical role of respiratory virus infection in acute otitis media. Pediatrics 1990;86:848-855
Web of Science | Medline

4
Hsiung GD. Picornaviridae. In: Hsiung GD, Fong CKY, Landry ML, eds. Hsiung's diagnostic virology. 4th ed. New Haven, Conn.: Yale University Press, 1994:119-40.

5
Pitkaranta A, Virolainen A, Jero J, Arruda E, Hayden FG. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 1998;102:291-295
CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

1
Paraskevi Maggina, Ioannis Christodoulou, Vassiliki Papaevangelou, Maria Tsolia, Nikolaos G Papadopoulos. (2009) Dendritic cells in viral bronchiolitis. Expert Review of Clinical Immunology 5:3, 271-282
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2
Lucien Corbeel. (2007) What is new in otitis media?. European Journal of Pediatrics 166:6, 511-519
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3
F. M. Chantzi, N. G. Papadopoulos, T. Bairamis, M. Tsiakou, N. Bournousouzis, A. G. Constantopoulos, G. Liapi, M. Xatzipsalti, D. A. Kafetzis. (2006) Human rhinoviruses in otitis media with effusion. Pediatric Allergy and Immunology 17:7, 514-518
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4
Y. Schönbeck, E.A.M. Sanders, A.W. Hoes, A.G.M. Schilder, Th.J.M. Verheij, E. Hak. (2005) Rationale and design of the prevention of respiratory infections and management in children (PRIMAKid) study. Vaccine 23:41, 4906-4914
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5
Niels Mygind, Jack Gwaltney Jr., Birgit Winther, J Hendley. 2003. The Common Cold and Its Relationship to Rhinitis, Sinusitis, Otitis Media, and Asthma. .
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