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Chapter 14 : Otitis Media

Author: Lauren O. Bakaletz1
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Affiliations: 1: Division of Molecular Medicine, College of Medicine and Public Health, The Ohio State University, and Children's Research Institute, Columbus, OH 43205
Content Type: Monograph
Publication Year: 2002

Category: Clinical Microbiology

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Abstract:

In all areas of the world, upper respiratory tract (URT) infections and their complicating sequelae are the leading causes of acute infectious morbidity. Otitis media (OM), or inflammation of the middle ear, is one of these complicating sequelae of URT infections and is indeed a major health care concern of childhood. This chapter discusses OM’s etiologic agents, animal models, and mechanisms of pathogenesis. Multiple mechanisms have been identified that serve as contributing factors in the synergistic relationship between the URT viruses and the primary bacterial pathogens of OM, and while each of these is a highly specific effect, all fall within the general category of compromise of airway defenses. The chapter reviews some of these mechanisms, such as viral effects on bacterial adherence and/or colonization, antibiotic efficacy, host immune functions, and rheological properties of mucus and mucociliary transport. We are continually adapting our treatment regimens for OM on the basis of newly acquired information and our improved understanding of the molecular mechanisms behind the pathogenesis of middle ear infections. Some of the ways this increased understanding has led to changes in our approaches to treat and/or prevent OM are reviewed. Good clinical evidence exists to believe that by eradicating the predisposing viral infection, one could have a significant effect on prevention of bacterial OM. Vaccine or treatment strategies that effectively inhibit the initial establishment of infection in the middle ear cleft will be particularly important in this regard.

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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Otitis Media
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Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.fig14-1
FIGURE 1

Number of patients per month with AOM ( = 4,524) (a) and respiratory virus infections (b to f ) during a 6-year study in the Turku University Hospital (Turku, Finland). (b) All virus infections ( = 961); (c) respiratory syncytial virus ( = 472); (d) adenovirus (= 197); (e) parainfluenza virus types 1, 2, and 3 (= 176); (f ) influenza A (unshaded) and influenza B (gray) viruses ( = 116). (Reprinted from [ ] with permission of the publisher.)

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FIGURE 1

Number of patients per month with AOM ( = 4,524) (a) and respiratory virus infections (b to f ) during a 6-year study in the Turku University Hospital (Turku, Finland). (b) All virus infections ( = 961); (c) respiratory syncytial virus ( = 472); (d) adenovirus (= 197); (e) parainfluenza virus types 1, 2, and 3 (= 176); (f ) influenza A (unshaded) and influenza B (gray) viruses ( = 116). (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 2

(A) Cumulative percentage of 38 ears (19 chinchillas) developing OME after i.n. inoculation of type 7F All ears with effusion yielded pneumococci on culture. (B) Cumulative percentage of 72 ears (36 chinchillas) developing OME and without effusion after i.n. inoculation of type 7F and influenza A virus. Symbols: ●, animals with pneumococcal OME; Δ, animals with pneumococcal and other culture-positive OME (other bacteria included [1 ear] and species [1 ear]); □, animals with culturepositive as well as sterile OME; ○, animals with all types of OME and OM without effusion. (Both panels are reprinted from [ ] with permission of the publisher.)

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FIGURE 2

(A) Cumulative percentage of 38 ears (19 chinchillas) developing OME after i.n. inoculation of type 7F All ears with effusion yielded pneumococci on culture. (B) Cumulative percentage of 72 ears (36 chinchillas) developing OME and without effusion after i.n. inoculation of type 7F and influenza A virus. Symbols: ●, animals with pneumococcal OME; Δ, animals with pneumococcal and other culture-positive OME (other bacteria included [1 ear] and species [1 ear]); □, animals with culturepositive as well as sterile OME; ○, animals with all types of OME and OM without effusion. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 3

Adherence of NTHI to chinchilla eustachian tube floor (a) or roof (b) mucus during AV infection. Symbols: ●, pharyngeal; ▪, mid-Eustachian tube; ▲, tympanic portion; *, significant difference compared with same day, same portion of ET roof, µ 0.05.) (c) Adherence of NTHI to chinchilla middle ear mucosal epithelium during adenovirus infection. (All panels are reprinted from [ ] with permission of the publisher.) Error bars indicate deviations.

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FIGURE 3

Adherence of NTHI to chinchilla eustachian tube floor (a) or roof (b) mucus during AV infection. Symbols: ●, pharyngeal; ▪, mid-Eustachian tube; ▲, tympanic portion; *, significant difference compared with same day, same portion of ET roof, µ 0.05.) (c) Adherence of NTHI to chinchilla middle ear mucosal epithelium during adenovirus infection. (All panels are reprinted from [ ] with permission of the publisher.) Error bars indicate deviations.

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 4

Histographic representation of number of A549 cells ( axis) expressing red fluorescence of PKH-26-labeled NTHI ( axis), as determined by flow cytometry (A549:NTHI = 1:100). (A) Background fluorescence of RSV-exposed (multiplicity of infection = 1, 24 h) or control A549 cells; (B and C) fluorescence of NTHI and NTHI attached to control or pRSV-exposed A549 cells. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 4

Histographic representation of number of A549 cells ( axis) expressing red fluorescence of PKH-26-labeled NTHI ( axis), as determined by flow cytometry (A549:NTHI = 1:100). (A) Background fluorescence of RSV-exposed (multiplicity of infection = 1, 24 h) or control A549 cells; (B and C) fluorescence of NTHI and NTHI attached to control or pRSV-exposed A549 cells. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 5

Comparison of nasopharyngeal carriage of nontypeable and in normal (□) and otitis-prone (▨) children during health (A) and during upper respiratory tract illness (B). , < 0.05; , < 0.001 ( ). (Reprinted from the [ ] with permission of the publisher.)

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FIGURE 5

Comparison of nasopharyngeal carriage of nontypeable and in normal (□) and otitis-prone (▨) children during health (A) and during upper respiratory tract illness (B). , < 0.05; , < 0.001 ( ). (Reprinted from the [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 6

Anatomy of the Eustachian tube and middle ear system. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 6

Anatomy of the Eustachian tube and middle ear system. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 7

Eustachian tube lumen on day 5 (a and b) and day 10 (c and d) after i.n. influenza virus inoculation showing mucoid secretions and cellular debris (hematoxylin and eosin stain; original magnification, ×400). (Reprinted from [ ] with permission of the publisher.)

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FIGURE 7

Eustachian tube lumen on day 5 (a and b) and day 10 (c and d) after i.n. influenza virus inoculation showing mucoid secretions and cellular debris (hematoxylin and eosin stain; original magnification, ×400). (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 8

Occurrence of AOM after the onset of URI in 250 episodes. Bar, number of cases on each day; line, cumulative force of morbidity. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 8

Occurrence of AOM after the onset of URI in 250 episodes. Bar, number of cases on each day; line, cumulative force of morbidity. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 9

Ciliary beat frequency of chinchilla Eustachian tube epithelium at sites near the tympanic or pharyngeal orifice following inoculation of influenza A virus. *, significant difference ( ≤ 0.01) from control. Error bars indicate standard deviations. (A) Transbullar inoculation; (B) i.n. inoculation. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 9

Ciliary beat frequency of chinchilla Eustachian tube epithelium at sites near the tympanic or pharyngeal orifice following inoculation of influenza A virus. *, significant difference ( ≤ 0.01) from control. Error bars indicate standard deviations. (A) Transbullar inoculation; (B) i.n. inoculation. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 10

Light micrographs of chinchilla Eustachian tube epithelium after i.n. inoculation of influenza A virus (original magnification, ×64). (A) Two days postinoculation, tympanic site. (B) At 4 days, pharyngeal site. Note focal loss of ciliated cells. (C) At 10 days, pharyngeal site. Note short, regenerating cilia. (D) At 28 days, pharyngeal site. Note normal appearance of epithelium. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 10

Light micrographs of chinchilla Eustachian tube epithelium after i.n. inoculation of influenza A virus (original magnification, ×64). (A) Two days postinoculation, tympanic site. (B) At 4 days, pharyngeal site. Note focal loss of ciliated cells. (C) At 10 days, pharyngeal site. Note short, regenerating cilia. (D) At 28 days, pharyngeal site. Note normal appearance of epithelium. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 11

(A) Change over time in ciliary activity of Eustachian tube mucosal epithelium after i.n. inoculation of AV type 1. Data represent means and standard deviations of at least 30 readings. (B) Change over time in ability of Eustachian tube to transport dye after i.n. inoculation of AV type 1. (Both panels are reprinted from [ ] with permission of the publisher.)

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FIGURE 11

(A) Change over time in ciliary activity of Eustachian tube mucosal epithelium after i.n. inoculation of AV type 1. Data represent means and standard deviations of at least 30 readings. (B) Change over time in ability of Eustachian tube to transport dye after i.n. inoculation of AV type 1. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 12

Cross-sections in mid-Eustachian tube 14 days after intranasal inoculation. (a) Note many vacuolated epithelial cells (vac) and those demonstrating late stages of intranuclear inclusions typical of AV. (b) Note marked goblet cell (*) hyperplasia. Bars = 50 µm. (Reprinted from [ ] with permission of the publisher.)

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FIGURE 12

Cross-sections in mid-Eustachian tube 14 days after intranasal inoculation. (a) Note many vacuolated epithelial cells (vac) and those demonstrating late stages of intranuclear inclusions typical of AV. (b) Note marked goblet cell (*) hyperplasia. Bars = 50 µm. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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FIGURE 13

(A) Percentage of nasal lavage specimens that were culture positive for NTHI in AV-compromised chinchillas that received either saline (shamimmunized) or antisera directed against one of two adhesin-based immunogens [LB1 or LPD-LB1 (f)] by passive transfer prior to i.n. challenge with either of two strains of NTHI (86-028NP or 1885MEE). (B) Percentage of ears that developed OM within each cohort of animals depicted in A. (Both panels are reprinted from [ ] with permission of the publisher.)

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FIGURE 13

(A) Percentage of nasal lavage specimens that were culture positive for NTHI in AV-compromised chinchillas that received either saline (shamimmunized) or antisera directed against one of two adhesin-based immunogens [LB1 or LPD-LB1 (f)] by passive transfer prior to i.n. challenge with either of two strains of NTHI (86-028NP or 1885MEE). (B) Percentage of ears that developed OM within each cohort of animals depicted in A. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
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Tables

Otitis Media
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Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-1
TABLE 1

Comparison of clinical and bacteriologic outcome of patients with AOM caused by bacteria alone or bacteria and virus

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10.1128/9781555817947/tab14-1.gif
Generic image for table
TABLE 1

Comparison of clinical and bacteriologic outcome of patients with AOM caused by bacteria alone or bacteria and virus

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-2
TABLE 2

Dye transport values for chinchillas injected transbullarly with influenza A/Alaska/6/77 virus

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10.1128/9781555817947/tab14-2.gif
Generic image for table
TABLE 2

Dye transport values for chinchillas injected transbullarly with influenza A/Alaska/6/77 virus

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-3
TABLE 3

Demographic information on 186 participants in influenza-OM trial

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10.1128/9781555817947/tab14-3.gif
Generic image for table
TABLE 3

Demographic information on 186 participants in influenza-OM trial

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-4
TABLE 4

Percentage of infants with AOM and SOM infections before, during, and after influenza season

10.1128/9781555817947/tab14-4_thmb.gif
10.1128/9781555817947/tab14-4.gif
Generic image for table
TABLE 4

Percentage of infants with AOM and SOM infections before, during, and after influenza season

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14

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