Ann 0101 Rhinal Laryngal99: 1990

RHINOVIRUS IN OTITIS MEDIA WITH EFFUSION MIKKO AROLA, MD THEDI ZIEGLER, PHD

HEIKKI PUHAKKA, MD

OLLI-PEKKA LEHTONEN, MD

OLLI RUUSKANEN, MD TURKU, FINLAND

We studied rhinovirus in the middle ear fluid of 61 children with subacute or chronic otitis media with effusion. Rhinovirus was recovered from the middle ear fluid of 5 children with subacute otitis media with effusion. The minimum duration of effusion was 32 to 60 days. Additionally, 1 patient had middle ear fluid that was positive for adenovirus. Bacterial pathogens were cultured from the middle ear fluid of 20 of 61 patients. Our finding that rhinovirus can be isolated from middle ear fluid after an asymptomatic period of several weeks suggests its possible role in the development of otitis media with effusion. KEY WORDS - adenovirus, otitis media with effusion, rhinovirus.

INTRODUCTION

tially 1 to 3 months before referral," and preoperatively there had been a visit to an otorhinolaryngologist (in general 2 to 3 weeks before operation), who confirmed the diagnosis. The presence of effusion was finally verified by myringotomy at the operation. The duration of the effusion was calculated from the initial diagnosis of OME, which can be considered as minimum duration of effusion.

Otitis media with effusion (OME) is regarded as a multifactorial disease process. Bacterial infection and eustachian tube obstruction are its best-understood pathogenetic factors. I Efforts to isolate viruses or detect viral antigens in middle ear effusion of subacute or chronic OME have so far been unrewarding,":" except for one adenovirus-positive case in 60 children. 5 Despite these poor results, increasing circumstantial evidence suggests that viruses may play a role in the causation of secretory otitis media."

There were 46 boys and 15 girls. Seven patients were less than 12 months of age, 29 between 1 and 3 years, and 25 patients more than 3 years of age (mean age, 3.2 years; range, 9 months to 12.6 years). The time from the last episode of acute otitis media diagnosed by a physician and from the last episode of upper respiratory tract infection was asked from the parents at the time of the operation. The mean interval between the last episode of acute infection and operation was 25 days (range, 8 to 90 days) for upper respiratory tract infection and 21 days (range, 8 to 90 days) for acute otitis media. Because 25 of the patients had been in close follow-up by an otorhinolaryngologist, the precise minimum duration of effusion could be given: in 25 patients the mean duration of the effusion was 57 days (range, 22 to 113 days). However, in all patients the effusion had been present for at least 3 weeks.

We recently managed to isolate rhinovirus in 8 % of middle ear effusions and in 18 % of nasopharyngeal mucus aspirates in patients with acute otitis media." These observations prompted us to study the role of rhinovirus in the development of OM£. PATIENTS AND METHODS

The study was carried out between November 1987 and January 1988. It included 100 consecutive children who were referred to an otorhinolaryngologist for subacute or chronic OME. During the preoperative 7 days, 35 patients had mild respiratory symptoms, ie, rhinorrhea and cough, reported by the parents; and further, four patients contracted acute otitis media. These 39 patients were thus excluded from the analysis, and 61 patients were left in the study. Otitis media with effusion was defined as the presence of asymptomatic middle ear effusion. The effusion was considered acute with less than 3 weeks' duration, subacute with 3 weeks' to 3 months' duration, and chronic with more than 3 months' duration. I The diagnosis of OME was initially made by the referring physician with pneumatic otoscopy. The patients had been followed ini-

Middle ear fluid samples were collected by myringotomy under general anesthesia for adenoidectomy (in 47 of 61 children) or for insertion of pressureequalizing tubes (in 58 of 61 children). Middle ear fluid was used for bacterial culture on sheep blood and MacLeod agar and incubated for 48 hours in a carbon dioxide atmosphere at 35°C. For virus isolation, a cotton swab was dipped in the middle ear fluid sample and placed in a vial containing 2 mL virus transport medium (0.5 % bo-

From the Departments of Pediatrics (Arola, Ruuskanen). Virology (Ziegler), and Otolaryngology (Puhakka), University of Turku, and the Department of Clinical Microbiology, Turku University Hospital (Lehtonen), Turku, Finland. Supported by grants from the Medical Council Academy of Finland, the Pediatric Research Foundation of Finland, and the Finnish Foundation for Research of Viral Diseases. REPRINTS - Mikko Arola, MD, Dept of Pediatrics, Turku University Hospital, 20520 Turku, Finland.

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Arola et al, Rhinovirus in Otitis Media

TABLE 1. PATIENTS WITH VIRUS ISOLATED FROM MIDDLE EAR EFFUSIONS

Sex

Age (mo)

Virus Isolation

M

12

Rhinovirus

M M F M

67 20 16 11

Rhinovirus Rhinovirus Rhinovirus Rhinovirus

F

17

Adenovirus

Bacterial Culture Streptococcus pneumoniae Negative Negative Negative Staphylococcus aureus Streptococcus pneumoniae

Preoperative Established Minimum Duration r:L Effusion ( ) 32 60 37

44 48 30

vine albumin in tryptose-phosphate broth containing antibiotics). The virus isolation specimens were immediately frozen on dry ice and stored at -70°C until processed. Virus isolation was done as described earlier, with some modifications. 8 One hundred microliters of each specimen was inoculated into duplicate roller-tube cultures of HeLa Ohio cells and of human fibroblasts. The cultures were stored in a roller device (12 revolutions per hour) at 33°C and examined microscopically every second day. After 6 days of incubation, blind passages were done ~f negative HeLa cultures, and the passages were mcu.bated for another week. Occasionally a second bhnd passage was done. Rhinovirus was identified by its typical cytopathogenic effect and lability to acid treatment. RESULTS

Respiratory viruses were isolated from the middle ear fluid of 6 of 61 (10 %) patients with OME: rhinovirus was isolated in five cases, and adenovirus in one case (Table 1). The mean time from the last episode of acute otitis media or symptomatic respiratory tract infection to sur~ical intervention was 38 days (range, 18 to 60 days) m the rhinovirus-positive group. The adenovirus-positive patient had her last preceding episode of acute otitis and respiratory tract infection 14 days before operation. The precise onset and duration of middle ear effusion are often unknown. Yet, reasonable assumptions can be made. The mean duration of recorded middle ear effusion was 42 days in the virus-positive group (Table 1). The appearance of the middle ear fluid was mucous in all of these patients, suggesting an extended duration of effusion. All patients with virus in the middle ear flui? r~ceive~ t~mpanostomy tubes. Ear discharge begmmng within a week postoperatively was reported in three of the six virus-positive patients. One of them had a negative middle ear fluid bacterial culture, one showed Streptococcus pneumoniae, and one showed Staphylococcus aureus, Middle ear effusion was present in 104 ears of the 61 patients at the time of operation. It was mucous

TABLE 2. BACTERIA ISOLATED FROM 61 MIDDLE EAR EFFUSIONS Strain

No. oj Isolates

%

11 5 4

18 8 7

2 41

~

Hemophilus injluenzae Staphylococcus aureus Streptococcus pneumoniae Branhamella catarrhalis N~iliw

3

On.e patient had concomitant H injluenzae and S pneumoniae, and one H injluenzae and S aureus.

in 98 (94 %) ears, serous in 2, and purulent in 4. Positive bacterial cultures from middle ear fluid were obtai?ed in 20 (33 %) of 61 patients (Table 2). Pos~operatIve otorrhea was reported in 14 (23 %) patients (24 ears). In 6 (43%) of 14 patients bacteria were already cultured in the middle ear fluid sample taken at the time of operation. Hemophilus inJluenzae was found in two samples, S pneumoniae in two, Branhamella catarrhalis in one, and S aureus in one. However, no significant differences were found in the rates of postoperative otorrhea in patients with middle ear fluid positive or negative for bacteria or viruses. DISCUSSION

Increasing ~vidence suggests that respiratory viruses play an Important pathogenetic role in acute otitis m~dia .. Four re~ent studies have found respiratory VIruS In the middle ear fluid of 11 % to 23 % of patients with acute otitis media. 7 . 9 - 1 1 On the ?ther hand, a~ute otitis media has been diagnosed ~n 57 % of respiratory syncytial virus (RSV), 35 % of I~fluenza A virus, 33 % of parainfluenza type 3 VIruS, and 30 % of adenovirus infections in hospitalized pediatric patients. 12 In a study of rhinovirus and acute otitis media

6

~e found rhinovirus in the nasopharynx of two p~­

tients at the time of diagnosis of acute otitis media. After 2 weeks, when tympanocentesis was done beca~se ?f poor ~esponse to antimicrobial therapy, rhinovirus was Isolated from the middle ear fluid. Unfortunately, no typing of the virus strains could be done to exclude reinfection by another virus strain. In the present study, we isolated viruses in the middle ear fluid of 10 % of patients with subacute or chronic OME. Rhinovirus was the most common virus isolated from the middle ear fluid samples. This may be explained by the fact that the study was carried out during the rhinovirus season. In addition, the isolation technique used has proved sensitive to rhinovirus from middle ear fluid." During the preceding 6 months RSV, parainfluenza 2, adenovirus, ~nd rhinovirus were the respiratory viruses present in the community. No influenza A or B was diagnosed in that time, and thus the virus isolation method used in the study was not adapted for them. We may have lost some cases of otitis media associated with RSV, since the isolation technique

Arola et al, Rhinovirus in Otitis Media

was not optimal for RSV and RSV antigens of middle ear fluid were not studied. The mean duration of recorded effusion in the middle ear of the virus-positive patients was 42 days, suggesting that a prolonged viral infection might induce OME. An acute respiratory tract infection was not the reason for the viral finding in middle ear fluid, since the mean duration from upper respiratory tract infection was 38 days. However, asymptomatic infection cannot be ruled out. In agreement with these observations, studies on local immunoglobulin A antibodies against respiratory viruses have suggested a possible previous viral middle ear infection in 20 % to 50 % of patients with OME. 13 . 14 The seasonal changes of posttympanostomy otorrhea rate suggest an effect due to extrinsic causes such as outbreaks of respiratory tract virus infections. 15 In 12 % to 21 % of cases, the middle ear fluid of asymptomatic children harbors bacterial pathogens similar to those identified in acute otitis;":" The

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most common bacterial finding in mucoid-appearing effusion of chronic otitis media is H influenzae. 18 We found pathogenic bacteria in 33 % of middle ear fluid samples of patients with OME. Of these, 30 % had purulent otorrhea after operation. Further, S aureus grew in 8 % of samples (Table 2). Some of these may have been contaminated, since the external ear canal had not been sterilized. The presence of pathogenic bacteria in a marked number of ears with postoperative purulent otorrhea suggests that it might be beneficial to perform Gram's stain on and to culture middle ear fluid samples from OME patients undergoing operations and to treat all positive cases with antibiotics for prevention of otorrhea. This approach, however, needs further study. Our data suggest that in some patients rhinovirus can be isolated from the middle ear fluid after an asymptomatic period of several weeks. The significance of a possible viral infection in the middle ear for the pathogenesis of subacute or chronic OME remains to be clarified.

REFERENCES 1. Bluestone CD, Klein JO. Otitis media in infants and children. Philadelphia, Pa: WB Saunders, 1988:1-3, 15-29.

syncytial virus and other viral pathogens in acute otitis media. J Pediatr 1982;101:16-20.

2. Fishman LZ, Lennette EH, Dannenberg TB. Indolent, or so-called serous otitis media. Including combined allergy and virus studies. Arch Otolaryngol 1960;72:25-30.

11. Chonmaitree T, Howie VM, Truant AL. Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media. Pediatrics 1986;77:698701.

3. Adlington P, Hooper WK. Virus studies in secretory otitis media. J Laryngol OtoI1980;94:191-6. 4. Sarkkinen H, Meurman 0, Puhakka H, Suonpaa J, Virolainen E. Failure to detect viral antigens in the middle ear secretions of patients with secretory otitis media. Acta Otolaryngol [Suppl] (Stockh) 1982(suppl 386):106-7. 5. Bellini MJ, Peel RN, Terry RM. Chlamydia: its influence in chronic secretory otitis media. J Laryngol Oto11988; 102:673-6. 6. Arola M, Ziegler T, Ruuskanen 0, Mertsola J, NantoSalonen K, Halonen P. Rhinovirus in acute otitis media. J Pediatr 1988;113:693-5. 7. Karma P, Paiva T, Kouvalainen K, et al. Finnish approach to the treatment of acute otitis media. Report of the Finnish Consensus Conference. Ann Otol Rhinol Laryngol 1987;96(suppl 129). 8. Larson HE, Reed SY, Tyrrell DAJ. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Viro11980; 5:221-9. 9. Sarkkinen H, Ruuskanen 0, Meurman 0, Puhakka H, Virolainen E, Eskola J. Identification of respiratory virus antigens in middle ear fluids of children with acute otitis media. J Infect Dis 1985;151:444-8. 10. Klein BS, Dollete FR, Yolken RH. The role of respiratory

12. Ruuskanen 0, Arola M, Putto-Laurila A, et al. Acute otitis media and respiratory virus infections. Pediatr Infect Dis J 1989; 8:94-9. 13. Meurman OH, Sarkkinen HK, Puhakka HJ, Virolainen ES, Meurman OH. Local IgA-class antibodies against respiratory viruses in middle ear and nasopharyngeal secretions of children with secretory otitis media. Laryngoscope 1980;90:304-11. 14. Yamaguchi T, Urasawa T, Kataura A. Secretory immunoglobulin A antibodies to respiratory viruses in middle ear effusion of chronic otitis media with effusion. Ann Otol Rhinol Laryngol 1984;93:73-5. 15. Gates GA, Avery C, Prihoda TJ, Holt GR. Post-tympanostomy otorrhea. Laryngoscope 1986;96:630-4. 16. Riding KH, Bluestone CD, Michaels RH, Cantekin EI, Doyle WJ, Poziviak CS. Microbiology of recurrent and chronic otitis media with effusion. J Pediatr 1978;93:739-43. 17. Mills RP, Uttley AHC, McIntyre MF. A bacteriological study of the middle ear and upper respiratory tract in children with chronic secretory otitis media. Clin Otolaryngol 1985;10: 335-41. 18. Karma P. Secretory otitis media - infectious background and its implications for treatment. Acta Otolaryngol [Suppl] (Stockh) 1988(suppI449):47-8.

Rhinovirus in otitis media with effusion.

We studied rhinovirus in the middle ear fluid of 61 children with subacute or chronic otitis media with effusion. Rhinovirus was recovered from the mi...
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