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. 2003;3(4):326–334. doi: 10.1007/s11882-003-0093-7

Prevention of otitis media caused by viral upper respiratory tract infection: Vaccines, antivirals, and other approaches

William J Doyle 1, Cuneyt M Alper 1
PMCID: PMC7088701  PMID: 12791210

Abstract

Otitis media (OM) imposes significant morbidity on the pediatric age group and a large financial burden on the general population. Because standard medical treatments are not highly efficacious in resolving the accompanying middle ear (ME) inflammation, a goal of current research is OM prevention. Past studies show that new episodes of OM are usually a complication of viral upper respiratory infection (vURI), and therefore, a rational approach to achieving that goal is to develop intervention strategies that target vURIassociated OM. However, past experiences with antibiotics show that, in the absence of well-defined treatment protocols that maximize expected efficacy, the adoption of prophylactic or active treatments for OM can have negative consequences for the patient and for the general population. In this review, we discuss the hypothesized mechanisms by which a vURI is translated into an acute OM episode and describe different strategies for aborting that process. Limitations to deployment of each strategy are outlined.

Keywords: Influenza, Respiratory Syncytial Virus, Otitis Medium, Xylitol, Fluticasone Propionate

References and Recommended Reading

  • 1.Freid VM, Makuc DM, Rooks RN. Ambulatory health care visits by children: principal diagnosis and place of visit. National Center for Health Statistics. Vital Health Stat. 1998;13:1–23. [PubMed] [Google Scholar]
  • 2.Mandel EM, Rockette HE, Bluestone CD, et al. Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children: results of a double blind, randomized trial. N Engl J Med. 1987;316:432–437. doi: 10.1056/NEJM198702193160803. [DOI] [PubMed] [Google Scholar]
  • 3.Giebink GS, Batalden PM, Le CT, et al. A controlled trial comparing three treatments for chronic otitis media with effusion. Pediatr Infect Dis J. 1990;9:33–40. doi: 10.1097/00006454-199001000-00008. [DOI] [PubMed] [Google Scholar]
  • 4.Teele DW, Klein JO, Chase C, et al. Otitis media in infancy and intellectual ability, school achievement, speech and language at age 7 years. Pediatr Inf Dis J. 1990;162:685–695. doi: 10.1093/infdis/162.3.685. [DOI] [PubMed] [Google Scholar]
  • 5.Klein JO. Otitis media. Clin Infect Dis. 1994;19:823–833. doi: 10.1093/clinids/19.5.823. [DOI] [PubMed] [Google Scholar]
  • 6.Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial drugs for acute otitis media: meta-analysis of 5400 children from thirty-three randomized trials. J Pediatr. 1994;124:355–367. doi: 10.1016/S0022-3476(94)70356-6. [DOI] [PubMed] [Google Scholar]
  • 7.Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ. 1997;314:1526–1529. doi: 10.1136/bmj.314.7093.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Gates GA. Cost-effectiveness considerations in otitis media treatment. Otolaryngol Head Neck Surg. 1996;114:525–530. doi: 10.1016/S0194-5998(96)70243-7. [DOI] [PubMed] [Google Scholar]
  • 9.Casselbrant ML, Kaleida PH, Rockette HE, et al. Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial. Pediatr Infect Dis J. 1992;11:278–286. doi: 10.1097/00006454-199204000-00004. [DOI] [PubMed] [Google Scholar]
  • 10.Duffy LC, Faden H, Wasielewski R, et al. Exclusive breastfeeding protects against bacterial colonization and day care exposure to otitis media [abstract] Pediatrics. 1997;100:E7–E7. doi: 10.1542/peds.100.4.e7. [DOI] [PubMed] [Google Scholar]
  • 11.Englund JA, Glezen WP. Passive immunization for the prevention of otitis media. Vaccine. 2000;19:S116–S121. doi: 10.1016/S0264-410X(00)00289-9. [DOI] [PubMed] [Google Scholar]
  • 12.Eskola J, Kilpi T, Palmu A, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001;344:403–409. doi: 10.1056/NEJM200102083440602. [DOI] [PubMed] [Google Scholar]
  • 13.Paradise JL, Bluestone CD, Colborn DK, et al. Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes. JAMA. 1999;282:945–953. doi: 10.1001/jama.282.10.945. [DOI] [PubMed] [Google Scholar]
  • 14.Uhari M, Kontiokari T, Koskela M, Niemela M. Xylitol chewing gum in prevention of acute otitis media: double blind randomized trial. BMJ. 1996;313:1180–1184. doi: 10.1136/bmj.313.7066.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Roos K, Hakansson EG, Holm S. Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ. 2001;322:210–212. doi: 10.1136/bmj.322.7280.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Varon E, Levy C, De La Rocque F, et al. Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections. Clin Infect Dis. 2000;31:477–481. doi: 10.1086/313981. [DOI] [PubMed] [Google Scholar]
  • 17.Heikkinen T, Ruuskanen O. Temporal development of acute otitis media and respiratory virus infections. Pediatr Infect Dis J. 1994;13:659–661. doi: 10.1097/00006454-199407000-00016. [DOI] [PubMed] [Google Scholar]
  • 18.Koivunen P, Kontiokari T, Niemela M, et al. Time to development of acute otitis media during an upper respiratory tract infection in children. Pediatr Infect Dis J. 1999;18:303–305. doi: 10.1097/00006454-199903000-00023. [DOI] [PubMed] [Google Scholar]
  • 19.Antonio SA, Don D, Doyle WJ, Alper CM. Daily home tympanometry to study the pathogenesis of otitis media. Ped Infect Dis J. 2002;21:882–885. doi: 10.1097/00006454-200209000-00022. [DOI] [PubMed] [Google Scholar]
  • 20.Henderson FW, Collier AM, Sanyal MA, et al. A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. N Engl J Med. 1982;306:1377–1383. doi: 10.1056/NEJM198206103062301. [DOI] [PubMed] [Google Scholar]
  • 21.Uhari M, Mantysaari K, Niemela M. A meta-analytic review of the risk factors for acute otitis media. Clin Infect Dis. 1996;22:1079–1083. doi: 10.1093/clinids/22.6.1079. [DOI] [PubMed] [Google Scholar]
  • 22.Pitkaranta A, Virolainen A, Jero J, et al. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics. 1998;102:291–295. doi: 10.1542/peds.102.2.291. [DOI] [PubMed] [Google Scholar]
  • 23.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. doi: 10.1056/NEJM199901283400402. [DOI] [PubMed] [Google Scholar]
  • 24.Buchman CA, Doyle WJ, Skoner DP, et al. Otologic manifestations of experimental rhinovirus infection. Laryngoscope. 1994;104:1295–1299. doi: 10.1288/00005537-199410000-00021. [DOI] [PubMed] [Google Scholar]
  • 25.Buchman CA, Doyle WJ, Pilcher O, et al. Nasal and otological effects of experimental respiratory syncytial infection in adults. Am J Otolaryngol. 2002;23:70–75. doi: 10.1053/ajot.2002.30634. [DOI] [PubMed] [Google Scholar]
  • 26.Buchman CA, Doyle WJ, Skoner DP, et al. Influenza A virus-induced acute otitis media. J Infect Dis. 1995;172:1348–1351. doi: 10.1093/infdis/172.5.1348. [DOI] [PubMed] [Google Scholar]
  • 27.Giebink GS. Otitis media: the chinchilla model. Microb Drug Resist. 1999;5:57–72. doi: 10.1089/mdr.1999.5.57. [DOI] [PubMed] [Google Scholar]
  • 28.Suzuki K, Bakaletz LO. Synergistic effect of adenovirus type 1 and nontypeable Haemophilus influenzae in a chinchilla model of experimental otitis media. Infect Immun. 1994;62:1710–1718. doi: 10.1128/iai.62.5.1710-1718.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Wadowsky RM, Mietzner SM, Skoner DP, et al. Effect of experimental influenza A virus infection on the isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynx of allergic and non-allergic adult subjects. Infect Immun. 1995;63:1153–1157. doi: 10.1128/iai.63.4.1153-1157.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Klein J, Chonmaitree T, Loosmore C, et al. Otitis media: a preventable disease? Proceedings from an international symposium organized by the Marcel Merieux Foundation, Veyrier-du-Lac, France, February 13–16, 2000. Pediatr Infect Dis J. 2001;20:473–481. doi: 10.1097/00006454-200105000-00002. [DOI] [PubMed] [Google Scholar]
  • 31.Moyse E, Lyon M, Cordier G, et al. Viral RNA in middle ear mucosa and exudates in patients with chronic otitis media with effusion. Arch Otolaryngol Head Neck Surg. 2000;126:1105–1110. doi: 10.1001/archotol.126.9.1105. [DOI] [PubMed] [Google Scholar]
  • 32.Liederman EM, Post JC, Aul JJ, et al. Analysis of adult otitis media: polymerase chain reaction versus culture for bacteria and viruses. Ann Otol Rhinol Laryngol. 1998;107:10–16. doi: 10.1177/000348949810700103. [DOI] [PubMed] [Google Scholar]
  • 33.Mattila PS, Nykanen A, Eloranta M, Tarkkanen J. CD45RO(+), L-selectin(-), CXCR4(+), CCR5(+) T lymphocytes: a lymphocyte phenotype found in the middle ear effusion. Int Immunol. 2000;12:1235–1243. doi: 10.1093/intimm/12.9.1235. [DOI] [PubMed] [Google Scholar]
  • 34.Chonmaitree T, Owen MJ, Howie VM. Respiratory viruses interfere with bacteriologic response to antibiotics in children with acute otitis media. J Infect Dis. 1990;162:546–549. doi: 10.1093/infdis/162.2.546. [DOI] [PubMed] [Google Scholar]
  • 35.Gura T. Innate immunity: ancient system gets new respect. Science. 2001;291:2068–20671. doi: 10.1126/science.291.5511.2068. [DOI] [PubMed] [Google Scholar]
  • 36.Hayden FG, Fritz R, Lobo MC, et al. Local and systemic cytokine responses during experimental human influenza A virus infection: relation to symptom formation and host defense. J Clin Invest. 1998;101:643–649. doi: 10.1172/JCI1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Matsuda K, Tsutsumi H, Okamoto Y, Chiba C. Development of IL-6 and TNF-α activity in nasopharyngeal secretions of infants and children during infection with respiratory syncytial virus. Clin Diag Lab Immunol. 1995;2:322–324. doi: 10.1128/cdli.2.3.322-324.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Gentile DA, Doyle WJ, Zeevi A, et al. Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in adults. Hum Immunol. 2003;64:93–98. doi: 10.1016/S0198-8859(02)00705-X. [DOI] [PubMed] [Google Scholar]
  • 39.Cohen S, Doyle WJ, Skoner DP, et al. Social ties and susceptibility to the common cold. JAMA. 1997;277:1940–1944. doi: 10.1001/jama.277.24.1940. [DOI] [PubMed] [Google Scholar]
  • 40.Doyle WJ, Skoner DP, Igarashi Y, et al. Pattern of nasal secretions during influenza virus infection. Rhinology. 1996;34:2–8. [PubMed] [Google Scholar]
  • 41.Skoner DP, Firman P, Gentile DA, Doyle WJ. Urine histamine metabolite elevations during experimental colds. Ann Allergy Asthma Immunol. 2001;87:303–306. doi: 10.1016/S1081-1206(10)62244-2. [DOI] [PubMed] [Google Scholar]
  • 42.Borish L, Rosenwasser LJ. Update on cytokines. J Allergy Clin Immunol. 1996;97:719–734. doi: 10.1016/S0091-6749(96)80146-1. [DOI] [PubMed] [Google Scholar]
  • 43.Sanico AM, Atsuta S, Proud D, Togias A. Dose-dependent effects of capsaicin nasal challenge: in vivo evidence of human airway neurogenic inflammation. J Allergy Clin Immunol. 1997;100:632–641. doi: 10.1016/S0091-6749(97)70167-2. [DOI] [PubMed] [Google Scholar]
  • 44.Baraniuk JN. Neuropeptides. Am J Rhinol. 1998;12:9–16. doi: 10.2500/105065898780707964. [DOI] [PubMed] [Google Scholar]
  • 45.Swarts JD, Alper CM, Seroky JT, et al. In vivo observation with MRI of middle ear effusion in response to experimental underpressures. Ann Otol Rhinol Laryngol. 1995;104:522–528. doi: 10.1177/000348949510400704. [DOI] [PubMed] [Google Scholar]
  • 46.Abramson JS, Mills EL, Giebink GS, Quie PG. Depression of monocyte and polymorphonuclear leukocyte oxidative metabolism and bactericidal capacity by influenza A virus. Infect Immun. 1982;35:350–335. doi: 10.1128/iai.35.1.350-355.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Skoner DP, Doyle WJ, Tanner EP, et al. Effect of rhinovirus 39 infection on immune and inflammatory parameters in allergic and non-allergic subjects. Clin Exper Allergy. 1995;25:561–567. doi: 10.1111/j.1365-2222.1995.tb01095.x. [DOI] [PubMed] [Google Scholar]
  • 48.Gentile D, Skoner D, Whiteside T, et al. Effect of influenza A virus infection on lymphocyte phenotype and function. J Allergy Clin Immunol. 1994;93:204–208. [Google Scholar]
  • 49.Hebda P, Alper CM, Doyle WJ, et al. Upregulation of mRNA for inflammatory mediators in middle ear mucosa in a rat model of infectious otitis media. Ann Otol Rhinol Laryngol. 1998;107:501–507. doi: 10.1177/000348949810700608. [DOI] [PubMed] [Google Scholar]
  • 50.Slagel KR: The Nose Knows: Sinusitis, Digestion and Appropriate SANUM Therapy. Explore 11, 2002. http://www.explorepub. com/articles/slagel_11_2.html. Accessed January 22, 2003.
  • 51.Doyle WJ, Alper CM, Buchman C, et al. Illness and otological change provoked by experimental upper respiratory virus infection. Laryngoscope. 1999;109:324–327. doi: 10.1097/00005537-199902000-00027. [DOI] [PubMed] [Google Scholar]
  • 52.Nokso-Koivisto J, Kinnari TJ, Lindahl P, et al. Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms. J Med Virol. 2002;66:417–420. doi: 10.1002/jmv.2161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Doyle WJ, Skoner DP, Hayden F, et al. Nasal and otologic effects of experimental influenza A virus infection. Ann Otol Rhinol Laryngol. 1994;103:59–69. doi: 10.1177/000348949410300111. [DOI] [PubMed] [Google Scholar]
  • 54.Alper CM, Doyle WJ, Skoner DP, et al. Pre-challenge antibodies moderate disease expression in adults experimentally exposed to rhinovirus strain hanks. Clin Infect Dis. 1998;27:119–128. doi: 10.1086/514634. [DOI] [PubMed] [Google Scholar]
  • 55.Heikkinen T, Ruuskanen O, Waris M, et al. Influenza vaccination in the prevention of acute otitis media in children. Am J Dis Child. 1991;145:445–448. doi: 10.1001/archpedi.1991.02160040103017. [DOI] [PubMed] [Google Scholar]
  • 56.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. doi: 10.1001/archpedi.1995.02170230067009. [DOI] [PubMed] [Google Scholar]
  • 57.Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N Engl J Med. 1998;338:1405–1412. doi: 10.1056/NEJM199805143382002. [DOI] [PubMed] [Google Scholar]
  • 58.Simoes EA, Groothuis JR, Tristram DA, et al. Respiratory syncytial virus-enriched globulin for the prevention of acute otitis media in high risk children. J Pediatr. 1996;129:214–219. doi: 10.1016/S0022-3476(96)70245-7. [DOI] [PubMed] [Google Scholar]
  • 59.The IMpact-RSV Study Group Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in highrisk infants. Pediatrics. 1998;102:531–537. doi: 10.1542/peds.102.3.531. [DOI] [PubMed] [Google Scholar]
  • 60.Washington Drug Letter: FDA Rejects Picovir For Lack of Drug Interaction Data. http://www.fdanews.com/pub/wdl/34_23/regulations/4706-1.html. Accessed January 22, 2003. June 10, 2002.
  • 61.Clot J. Pharmacology of ribosomal immunotherapy. Drugs. 1997;53:33–36. doi: 10.2165/00003495-199700541-00009. [DOI] [PubMed] [Google Scholar]
  • 62.Pitcaranta A, Hayden FG. What’s new with common colds? Complications and management. Infect Med. 1998;15:117–128. [Google Scholar]
  • 63.Walker JB, Hussey EK, Treanor JJ, et al. Effects of the neuraminidase inhibitor zanamavir on otologic manifestations of experimental human influenza. J Infect Dis. 1997;176:1417–1422. doi: 10.1086/514136. [DOI] [PubMed] [Google Scholar]
  • 64.Doyle WJ, Skoner DP, Alper CM, et al. Effect of rimantadine treatment on clinical manifestations and otological complications in adults experimentally infected with influenza A (H1N1) virus. J Infect Dis. 1998;117:1260–1265. doi: 10.1086/515294. [DOI] [PubMed] [Google Scholar]
  • 65.Geibink GS, Ripley ML, Wright PF. Eustachian tube histopathology during experimental influenza A virus infection in the chinchilla. Ann Otol Rhinol Laryngol. 1987;96:199–206. doi: 10.1177/000348948709600212. [DOI] [PubMed] [Google Scholar]
  • 66.Buchman CA, Swarts JD, Panagiotous N, et al. Otologic and systemic manifestations of experimental influenza A virus infection in the ferret. Otolaryngol Head Neck Surg. 1995;112:572–578. doi: 10.1016/S0194-5998(95)70213-X. [DOI] [PubMed] [Google Scholar]
  • 67.Sanyal MA, Henderson FW, Stempel EC. Effect of upper respiratory tract infection on Eustachian tube ventilatory function in the preschool child. J Pediatr. 1980;97:11–15. doi: 10.1016/S0022-3476(80)80121-1. [DOI] [PubMed] [Google Scholar]
  • 68.Turner RB, Darden PM. Effect of topical adrenergic decongestants on middle ear pressure in infants with common colds. Pediatr Infect Dis J. 1996;15:621–624. doi: 10.1097/00006454-199607000-00012. [DOI] [PubMed] [Google Scholar]
  • 69.Ruohola A, Heikkinen T, Waris M, et al. Intranasal fluticasone propionate does not prevent acute otitis media during viral upper respiratory infection in children. J Allergy Clin Immunol. 2000;106:467–471. doi: 10.1067/mai.2000.108912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Tapiainen T, Luotonen L, Kontiokari T, et al. Xylitol administered only during respiratory infections failed to prevent acute otitis media. Pediatrics. 2002;109:E19–E19. doi: 10.1542/peds.109.2.e19. [DOI] [PubMed] [Google Scholar]
  • 71.Fogle-Hansson M, White P, Hermansson A, Prellner K. Short-term penicillin-V prophylaxis did not prevent acute otitis media in infants. Int J Pediatr Otorhinolaryngol. 2001;7(59):119–123. doi: 10.1016/S0165-5876(01)00477-3. [DOI] [PubMed] [Google Scholar]
  • 72.Maeda S, Yamada Y, Nakamura H, Maeda T. Efficacy of antibiotics against influenza-like illness in an influenza epidemic. Pediatr Int. 1999;41:274–276. doi: 10.1046/j.1442-200x.1999.01069.x. [DOI] [PubMed] [Google Scholar]
  • 73.Heikkinen T, Ruuskanen O, Ziegler T, et al. Short-term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media. J Pediatr. 1995;126:313–316. doi: 10.1016/S0022-3476(95)70569-4. [DOI] [PubMed] [Google Scholar]
  • 74.Verdaguer N, Blaas D, Fita I. Structure of human rhinovirus serotype 2 (HRV2) J Mol Biol. 2000;300:1179–1194. doi: 10.1006/jmbi.2000.3943. [DOI] [PubMed] [Google Scholar]
  • 75.Casselbrant ML, Mandel EM, Fall PA, et al. The heritability of otitis media: a twin and triplet study. JAMA. 1999;282:2125–2130. doi: 10.1001/jama.282.22.2125. [DOI] [PubMed] [Google Scholar]
  • 76.Gentile DA, Zeevi A, Skoner DP, Doyle WJ. Modulation of RSV infection in infants by cytokine genotype. Hum Immunol. 2002;64:338–344. doi: 10.1016/S0198-8859(02)00827-3. [DOI] [PubMed] [Google Scholar]

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