The presence or absence of signs and symptoms and findings on the otoscopic examination provides the basis for diagnosis of the different types of otitis media.
Proper treatment depends on differentiation between acute otitis media (AOM) and otitis media with effusion.
The highest incidence of otitis media occurs between the ages of 6 and 11 months and decreases with age. Risk factors include both host and environmental factors.
Disease may be prevented through use of vaccines and risk factor reduction.
For children 6 months to 23 months of age with unilateral nonsevere AOM and those 2 years and older with unilateral or bilateral nonsevere AOM, published guidelines provide the option of observing rather than treating with antibiotics immediately.
Antihistamines and steroids are ineffective for the treatment of otitis media.
Tympanostomy tube insertion is effective in reducing recurrent episodes of otitis media and persistent middle ear effusion.
Adenoidectomy is not recommended for the initial surgical treatment of otitis media unless nasal obstruction is present but is recommended for children in whom a repeat surgical procedure is needed.
Careful follow-up is needed to identify complications and sequelae of otitis media as well as of its treatment.
Otitis media is not only a disease of modern times; it has been a major health problem in many societies. In the 8th century, the most common approach to healing was water from wells named after various saints. Otitis media is in general a childhood disease, but occurs in adolescents and adults. In most children it resolves with anatomic and physiologic changes with growth. Until the condition has resolved, it may affect balance, hearing, and speech and language development and cause poor school performance. This disease affects not only the child but the whole family, from an economic as well as a societal standpoint. It is more than the cost for medicine or visits to the doctors; enduring sleepless nights due to a crying child, having to take off from work to stay home with the child, and taking the child to the doctors can be very stressful for the family. The cost for medical and surgical therapy for otitis media in children 5 years of age or younger is estimated at $5 billion annually in the United States.
Definition, Symptoms, and Signs
Although considered to constitute a continuum of disease, otitis media can be subclassified into acute otitis media (AOM) and otitis media with effusion (OME) on the basis of signs and symptoms. Because the treatments for AOM and for OME differ, it is important to accurately diagnose the two conditions. AOM generally is characterized by rapid onset of signs and symptoms of inflammation in the middle ear accompanied by middle ear effusion (MEE). Signs of inflammation include bulging or fullness of the tympanic membrane (TM), erythema of the TM, and acute perforation of the TM with otorrhea. Symptoms include otalgia, irritability, and fever. OME, on the other hand, is defined as MEE without signs and symptoms of acute inflammation as found in AOM.
In addition to the examination of the ears, a proper head and neck examination is invaluable, because it may identify conditions that may predispose the patient to otitis media. Facial features should be assessed for craniofacial anomalies such as those of Down syndrome and Treacher Collins syndrome. Examination of the oropharynx may show a bifid uvula or a cleft palate. Hypernasality indicates velopharyngeal insufficiency, whereas hyponasality may be caused by obstructing adenoids or nasal obstruction due to nasal polyposis or deviated septum.
Pneumatic otoscopy is the primary diagnostic tool to evaluate the status of the middle ear, because it allows assessment of the TM and its mobility. The normal TM is translucent and concave and moves briskly with application of positive and negative pressure. A visible landmark is the handle (manubrium) of the malleus, which is attached to the TM, with the umbo in the center of the TM. To adequately visualize the TM, the external ear canal must be cleared of cerumen and debris. The assessment of the TM should note position , color , degree of translucency , and mobility . To ascertain the mobility of the TM, a good airtight seal must be obtained between the speculum and the ear canal. The largest speculum that fits comfortably should be used. A bulb through which air is puffed should be attached to the otoscope, allowing for visualization of TM mobility. Reduced or no mobility of the TM indicates loss of compliance of the TM, either as a result of effusion in the middle ear or from increased stiffness due to scarring or increased thickness of the TM. Total absence of mobility of the TM may also be due to an opening in the TM either as a perforation or a patent tympanostomy tube. Other features, such as fluid levels or bubbles, may be more easily discerned with movement of the TM. The position of the TM ranges from severely retracted to bulging. Mild to moderate retraction indicates negative pressure, MEE, or both, whereas a severely retracted TM usually is associated with effusion. Fullness and bulging of the TM are caused by increased pressure or fluid, or both, in the middle ear. Opacification of the TM may be caused by thickening or scarring or presence of MEE. A red but translucent TM is a typical finding in a crying or sneezing infant, secondary to engorgement of blood vessels in the TM. On the other hand, a “red” TM that is full or bulging often is a sign of AOM. A pink, gray, yellow, or blue retracted TM with reduced or no mobility usually is seen with OME. Myringitis is inflammation of the TM without fluid in the middle ear. Use of an operating microscope may clarify features seen on otoscopy, and visualization of scarring and atrophy of the TM may be enhanced.
Immittance Testing (Tympanometry)
Immittance testing is an excellent adjunct to the assessment of middle ear status and the management of otitis media. When otoscopic evaluation is inconclusive or difficult to perform, tympanometry can be very useful in evaluating ear disease in children older than 6 months of age. It is easy to perform and most often is well accepted by the patient. It has been used for school screening as well as in pediatricians’ offices. It also is valuable for documentation of middle ear status over time with repeat testing. A small probe which emits a tone is placed in the ear canal with an airtight seal. The tympanogram is obtained by plotting the immittance (acoustic energy of the reflected tone) of the middle ear as a function of varying pressure in the external ear canal, ranging from −400 to +200 daPa (decapascals). The instrument provides measures such as peak compensated (static) admittance, tympanometric peak pressure, acoustic reflex, and tympanometric width (TW) (a measure of gradient). A flat or rounded pattern (TW >350 daPa) with a small ear canal volume indicates MEE, whereas a flat pattern with a large ear canal volume suggests a perforation or a patent tympanostomy tube. In a normal air-filled middle ear with equal pressure on both sides of the TM, the peak pressure of the tympanogram is 0 daPa. Algorithms have been developed to determine the presence or absence of MEE, some combining pneumatic otoscopy and tympanometry. The following set of criteria uses TW and otoscopy to categorize middle ear status :
TW < 150 daPa = no OME
TW > 350 daPa = OME
TW 150 to 350 daPa = presence or absence of OME is determined by otoscopy
Other methods of ascertaining middle ear status have been investigated, including spectral gradient acoustic reflectometry and ultrasound evaluation, but they have been found to have limitations; acoustic reflectometry may be useful for screening.
MEE usually results in a mild to moderate conductive hearing loss. The assessment of hearing is essential to management, because hearing impairment can predispose the affected child to delays in speech and language development and may later affect school performance. Audiometry should be used to determine specific management strategies, with a more aggressive approach considered in children with significant hearing impairment.
Behavioral audiometry requires cooperation of the child with the examination, and the test is adapted to the age of the child. Visual reinforcement audiometry is used for children 6 months to 2 years of age and involves presentation of a sound stimulus in the sound field with observation of the child’s conditioned head turn response. This reaction is rewarded with a visual reinforcement such as an animated toy. Play audiometry , for children older than 2 years, is similar to conventional audiometry (for children >5 years), but the child places toys in a bucket rather than raising a hand to acknowledge hearing the sound. Hearing thresholds are determined at 0.25, 0.5, 1, 2, 4, and 8 kHz and may be ear-specific or in the sound field, depending on the age of the child.
Auditory brainstem response (ABR) and transient-evoked otoacoustic emissions are excellent methods for testing children who do not cooperate with behavioral hearing evaluation because of very young age or developmental delay. Except for infants young enough to be tested during natural sleep, sedation or general anesthesia is usually necessary for ABR testing in younger children. Three electrodes are placed (forehead and each mastoid process) to record the response to clicks of 2000 to 4000 Hz or pure-tone burst. The ABR consists of five to seven vertex-positive waves. Waves I to III presumably reflect activity of the auditory centers in the eighth nerve fibers and pons. Waves IV and V reflect auditory centers in the mid pons to rostral pons and caudal midbrain, respectively; the source of activity from waves VI and VII is less certain. The ABR reflects auditory neural electrical responses that are adequately correlated to behavioral hearing thresholds. However, a normal response on the ABR suggests only that the auditory system up to the midbrain level is responsive to the stimulus employed, and thus does not guarantee normal hearing.
Otoacoustic emissions testing measures cochlear function (outer hair cells) and is a means of objective assessment of auditory function. It commonly is used for newborn hearing screening because it is fast and easy to perform. It is excellent for testing children who do not cooperate with behavioral testing. MEE may confound the results. Therefore, if the otoacoustic emissions are absent, immittance testing should be performed to assess the middle ear. For children who “fail” otoacoustic emissions testing, follow-up audiologic testing with ABR must be done to assess the type and degree of hearing loss.
Pathophysiology and Pathogenesis
The pathophysiology of otitis media is multifactorial, with various overlapping factors ( Fig. 16-1 ).
Eustachian Tube Function
The eustachian tube in the infant is shorter, wider, and more horizontal than in the adult, which accounts for the high rate of otitis media in infants and children. By the age of 7 years, when the tube has a more adult configuration, the prevalence of otitis media is low. The three physiologic functions of the eustachian tube are (1) pressure regulation (ventilation), (2) protection , and (3) clearance (drainage). Of these three functions, pressure regulation is the most important ( Fig. 16-2 ). Middle ear pressure is equilibrated to atmospheric pressure through active intermittent openings of the eustachian tube caused by contraction of the tensor veli palatini muscle during swallowing, jaw movements, and yawning. If active function is impaired, negative pressure will develop in the middle ear. Pressure regulation can be impaired by failure of the opening mechanism ( functional obstruction ) or anatomic ( mechanical obstruction ). Using a pressure chamber, Bylander and associates evaluated eustachian tube function in children and adults who were considered otologically normal with intact TMs. Although only 5% of the adults were not able to equilibrate negative middle ear pressure, as many as 35.8% of the children could not equilibrate negative pressure. Children 3 to 6 years of age performed worse than children 7 to 12 years of age. These studies indicate that even apparently otologically normal children have worse eustachian tube function than adults do, but function does improve with age, paralleling the decrease in the incidence of otitis media. Stenström and colleagues tested eustachian tube function in 50 otitis-prone children and 49 children with no history of AOM (control group) using a pressure chamber. The otitis-prone children had significantly poorer active tubal function than the normal control subjects, suggesting that recurrent AOM is the result of functional obstruction of the eustachian tube.
In ears with normal eustachian tube function, the eustachian tube is collapsed when at rest, which protects the middle ear from nasopharyngeal sound pressure and reflux of secretions from the nasopharynx. The clearance of secretions produced within the middle ear into the nasopharynx is provided via the mucociliary system and through the “pumping action” of the eustachian tube during closing. The passive closing of the tube is initiated at the middle ear end of the eustachian tube and progresses toward the nasopharyngeal end, facilitating removal of the secretions.
Before the year 2000, studies in the United States reported that Streptococcus pneumoniae was the single most common bacterial pathogen in AOM, followed by Haemophilus influenzae and Moraxella catarrhalis ; Streptococcus pyogenes and other miscellaneous bacteria accounted for just a few cases. From ears with chronic OME, H. influenzae was the single most common pathogen, with S. pneumoniae , M. catarrhalis , and other bacteria accounting for a small percentage of cases each. Data obtained during the 1980s from a single institution are shown in Figure 16-3 . There was great hope that the introduction and subsequent use of the heptavalent conjugated pneumococcal vaccine (PCV7) Prevnar for infants and young children, licensed in the United States in 2000, would lead to a substantial decrease in AOM. However, data from vaccine trials conducted in California and Finland revealed only a 7.8% and a 6% relative risk reduction, respectively, in AOM. Casey and Pichichero examined the experience of children in a suburban Rochester, New York, practice in the years 2001 to 2003 (after the introduction of PCV7) compared with the years 1995 to 2000 and reported a 24% decrease in persistent AOM and AOM treatment failures. These investigators also reported a decrease in recovery of S. pneumoniae from the ears of such children and an increase in H. influenzae . In 2010, the same group reported that 6 to 8 years after widespread use of the vaccine, S. pneumoniae vaccine serotypes were not found in middle ear fluid of vaccinated children; H. influenzae remained a major pathogen of AOM. McEllistrem and coworkers looked at middle ear cultures obtained between 1999 and 2002 at five institutions. They reported that the percentage of AOM episodes due to non-PCV7 serogroups increased after 2000, from 12% in 1999 to 32% in 2002, and the nonvaccine serotypes were more frequent in those who received more than one dose of vaccine. The frequency of penicillin nonsusceptible strains in the vaccine and nonvaccine serotypes remained unchanged.
Nasopharyngeal carriage also was examined. Pelton and associates enrolled 275 infants and children 2 to 24 months of age in a surveillance study in which nasopharyngeal swabs or nasal washes were obtained at all well-child visits and at visits for AOM. From 2000 to 2003, these workers noted a decrease in vaccine serotypes with an increase in nonvaccine serotypes. Tracking antimicrobial susceptibility, they found that the MIC50 and the MIC90 for amoxicillin were stable until the 6-month period from October 2002 to March 2003, when they both increased significantly. Jacobs and associates examined the nasopharyngeal flora in children undergoing tympanostomy tube placement in March 2004 to March 2005 and also found a decrease in vaccine serotypes with a concomitant increase in nonvaccine serotypes, especially strain 19A, many of which were antibiotic-resistant strains.
A new 13-valent (PCV13) pneumococcal vaccine, Prevnar 13, was approved in the United States in 2010 and has replaced the 7-valent vaccine. The serotypes 1, 3, 5, 6A, 7F, and 19A are included in addition to the PCV7 strains. These data point to a changing bacteriology and the need for continued surveillance. A remarkable decrease in serious disease has occurred with the use of the newer pneumococcal vaccines, but the impact on otitis media continues to evolve.
Bacterial biofilms are sessile communities of interacting bacteria attached to a surface. They are encased in a protective matrix of exopolysaccharides rather than living in a motile “planktonic” or free-floating state. The exopolysaccharide matrix provides protection from phagocytosis and other host defense mechanisms by preventing accessibility by immunoglobulins and complement. The reduced metabolic rate of bacteria in the biofilm renders them resistant to antimicrobial treatment. The bacterial community relies on a complex intracellular communication system that provides for organized growth characteristics known as “quorum sensing.” Biofilms have been known to exist on hard surfaces such as metal pipes or teeth. However, recent animal and human studies have suggested that biofilms can also be isolated from the middle ear. Post and coworkers, using polymerase chain reaction (PCR) methodology, found evidence of bacteria in 48% of culture-negative MEE specimens from children undergoing tympanostomy tube insertion for chronic OME. Hall-Stoodley and colleagues obtained confocal laser scanning microscopy images from the middle ear mucosa of 26 children scheduled for tympanostomy tube insertion for recurrent or persistent otitis media and 8 control subjects (3 children and 5 adults) who underwent cochlear implantation. Generic stains and species-specific probes for H. influenzae , S. pneumoniae , and M. catarrhalis were used to evaluate biofilm morphology. Mucosal biofilms were visualized in 92% of the mucosa from children with chronic and recurrent otitis media but were not observed in any of the 8 control subjects. The investigators suggested that the findings supported the hypothesis that chronic middle ear disease is biofilm-related. Biofilms also have been identified in the nasopharynx of children with otitis media, and it was suggested that the biofilm may act as a reservoir for bacterial pathogens resistant to antibiotics. Mechanical debridement of nasopharyngeal biofilms may explain the observed clinical benefit associated with adenoidectomy in subsets of pediatric patients.
Until the introduction of PCR, viruses were not considered a major factor in the etiology of otitis media, probably because of the technical difficulties in isolating the viruses. Using PCR techniques, however, it has been possible to identify respiratory syncytial virus (RSV), influenzavirus, adenovirus, parainfluenza virus, and rhinoviruses in MEE. There is strong evidence that viruses have a crucial role in the development of AOM. In a majority of children, viral infection of the upper respiratory tract mucosa initiates the whole cascade of events that finally leads to the development of AOM, and AOM may be regarded as a complication of a preceding or concomitant viral infection. In a study of 60 children (in 24 families) who were followed from October 2003 through April 2004 by daily parental recording of illness signs, weekly pneumatic otoscopy and viral PCR analysis of nasal secretions collected during “colds” or when MEE was noted, or from enrolled siblings without these conditions, one or more viruses were identified from 73% of secretions collected during a cold but only 18% collected at a time without a cold. Of 93 episodes of otitis media, 70% occurred during a cold, and nasal secretions from 77% of children at the time of these episodes were positive for virus. Alper and colleagues reported that when a virus was isolated from the nasopharynx with or without a cold, an associated OM episode was classified as AOM in 8% of rhinovirus detections, 33% of RSV detections, and 38% of influenza A virus detections. Chonmaitree and coworkers diagnosed AOM in 37% of upper respiratory infection (URI) episodes and OME in 24% of episodes in a cohort of 6-month to 3-year-old children. Rhinovirus and adenovirus were most commonly detected during a URI, but rhinovirus was associated with a lower rate of OM than were other viruses.
Allergy and Immunology
Even though allergy is considered to play a role in the pathogenesis of otitis media, the causal mechanism is not understood, and well-controlled studies to prove the efficacy of antiallergic medication in the treatment of OM are lacking. Several mechanisms by which allergy may cause otitis media have been suggested: (1) the middle ear is a “shock organ” (target); (2) allergy may induce inflammatory swelling of the eustachian tube mucosa; (3) allergies produce inflammatory obstruction of the nose; and (4) bacteria-laden allergic nasopharyngeal secretions may be aspirated into the middle ear. The last three mechanisms involve an association between allergy and abnormal eustachian tube function. Prospective studies have reported a relationship between upper respiratory tract allergy and eustachian tube obstruction in a series of provocative, intranasal allergen–inhalation challenge studies.
More recent studies focus on the analysis of the inflammatory markers in MEE to determine the role of allergy. Both TH1 and TH2 inflammatory patterns in helper T cells have been found in OME. TH1 cytokines antagonize allergic inflammation and play a key part in the defense against viruses and intracellular pathogens, whereas TH2 cytokines promote immunoglobulin E (IgE) production, eosinophil growth, and mucus production. The chemoattractant cytokine RANTES ( r egulated upon a ctivation, n ormal T cell– e xpressed and s ecreted) and eosinophilic cationic protein (ECP), signs of a TH2 process, were assessed in MEE samples from 25 children with allergy and 20 nonallergic children who were 5 to 11 years old at the time of tympanostomy tube insertion. RANTES and ECP levels were significantly higher in the MEE samples from children with allergy than in children without allergy ( P < .01 and < .05, respectively). A positive correlation also was found between RANTES and ECP in MEE ( P < .01) in children with allergy, which suggests that allergy is a contributing factor in the pathogenesis of otitis media.
Children with major immune deficiencies may have recurrent otitis media as part of their overall clinical picture, but most otitis-prone children may have only a subtle immunologic abnormality that predisposes them to recurrent infections. The three major pathogens of otitis media— S. pneumoniae , H. influenzae , and M. catarrhalis— frequently colonize the nasopharynx. There are many strains of these organisms, and among the different strains are heterologous surface (strain-specific) antigens and conserved antigens. Conserved antigens induce broadly protective antibodies, whereas strain-specific antigens induce limited protection. Otitis-prone children may display strain-specific immunity but fail to develop a broadly protective antibody response, which makes them susceptible to recurrent and persistent otitis media.
Recurrence of bilateral OME after tympanostomy tube insertion was more likely in children with poor eustachian tube function and low IgA or low IgG2 and decreased levels of mannose-binding lectin than in children with poor tubal function and high IgA and IgG2 measured at the time of tube insertion. This suggests that an interaction between various immune factors may increase the risk for the development of otitis media.
In 2002, Tasker and associates reported finding pepsin/pepsinogen, using enzyme-linked immunosorbent assays, in 90.8% of 65 MEE samples obtained at the time of myringotomy in children. The pepsin-pepsinogen levels ranged from 0.8 to 213.9 µg/mL, which is 1000 times higher than serum levels. Using a sensitive and specific pepsin assay, pepsin activity was detected in 14.4% of 152 subjects undergoing tympanostomy tube insertion. The levels of pepsin ranged from 13 to 687 ng/mL. Crapko and associates also identified pepsin activity in the middle ear fluid in 60% of 20 subjects also undergoing tympanostomy tube insertion. In this group of children the pepsin levels ranged from 80 to 1000 ng/mL. In 2008, investigators reported finding pepsin in the middle-ear cleft of 20% of children undergoing tympanostomy tube insertion for OM and in 1.4% of children undergoing cochlear implant without a history of OM. The latter studies have shown that pepsin is identified less frequently and at lower levels, which may be due to differences in methodology. However, one can conclude from these studies that gastroesophageal reflux may be a causative factor in otitis media, with a potential role for antireflux therapy in the treatment of otitis media in some children. Adequately controlled trials have not yet been done.
Incidence and Prevalence
Otitis media is considered a worldwide pediatric health care problem. The Early Childhood Study–Birth Cohort, a nationally representative longitudinal study of more than 8000 children born in 2001, showed that otitis media was diagnosed in 39% of children by 9 months and 62% of children by 2 years of age. Although the highest incidence of otitis media is in young children, it also occurs in older children, adolescents, and adults. The Oslo Birth Cohort enrolling infants born in a 15-month period in 1992 to 1993 found that 13% of 10-year-olds had at least one episode of otitis media in the previous 12 months. In the United States, it was reported that of 22 million visits annually to physicians for AOM, 4 million were by patients 15 years and older. Recent data collected from 1997 to 2006 in the United States to assess demographic disparity among children with recurrent episodes of AOM (3 or more episodes reported by parents during the past 12 months) reported an average annual recurrent OM prevalence in children younger than 19 years (mean age, 8.6 years) of 6.6% over the 10-year period. Recurrent episodes occurred more often in children who were white (7.0%) or living below the poverty level (8%) but were reported less often in children who were uninsured (5.4%). Those with insurance had a slightly higher rate of recurrent OM (6.4%), probably because they had better access to care. Multivariate analysis showed that those living below the poverty level were at increased risk of recurrent OM, whereas black, Hispanic, and other racial groups were less likely to have recurrent OM than white children, possibly due to less access to care, resulting in underdiagnosed episodes of OM.
Acute Otitis Media
Most children experience at least one episode of AOM during their childhood. The cumulative incidence of the first episode of AOM based on studies from various countries ranges from 19% to 62% by age 1 year and 50% to 84% by 3 years of age ( Fig. 16-4 ). In a majority of these studies, the peak incidence of AOM was during the first 6 to 12 months of life. The incidence decreases with age, and by the age of 7 years, few children experience episodes of AOM. Recurrent episodes of AOM are common in young children. By 6 months of age, 20% have had two or more episodes. Occurrence of three or more episodes of AOM by the ages of 1, 3, 5, and 7 years has been documented in 10% to 19%, 50%, 65%, and 75% of children, respectively. Occurrence of six or more episodes of AOM was documented in 39% of children by the age of 7 years.
Otitis Media with Effusion
It may be difficult to determine the “true” incidence of OME because, by definition, OME is asymptomatic. Furthermore, most screening studies determine the presence of MEE without differentiating between AOM and OME. Also, a short time between observations is needed for precise assessment of the onset and time to resolution of each new episode of OME, because approximately 65% of OME episodes in children 2 to 7 years of age resolve within 1 month. Monthly examinations with otoscopy and tympanometry in 2- to 6-year-old children in a day-care center in Pittsburgh revealed MEE at least once in 53% to 61% of the children. Lous and Fiellau-Nikolajsen found an incidence of MEE of 26% in 7-year-old children followed monthly for 1 year using tympanometry.
The point prevalence of MEE from different countries shows a wide variation, depending on the age of the child, season of the year, and type of assessment. Thus, it must be emphasized that comparison of outcomes between studies will require careful evaluation of study methodology, as well as caution in drawing conclusions. However, nearly all children had experienced at least one episode by the age of 3 years.
Trend over Time
The annual prevalence of OM diagnosis has been tracked since 1997 in the United States as part of Healthy People 2010. The overall diagnosis of OM declined in children and adolescents by 27% between 1997 and 2007 from 345 to 247 per 1000 children younger than 18 years. Children younger than 3 years had the highest rates of OM based on surveys from ambulatory care visits to physician offices, hospital outpatient departments, and hospital emergency departments. In these children the OM rates declined by 38% from 1160 per 1000 children in 1997 to 840 in 2006 and 724 in 2007. In contrast to the youngest children (<3 years) the rates of OM diagnosis among children aged 3 to 5 years and 6 to 17 years increased from 275 to 316 and from 70 to 107, respectively, between 2006 and 2007. The investigators attributed the rate increase to possible sampling errors but also to infections with serotypes not included in the pneumococcal vaccine.
A decline in the incidence of otitis media also has been reported from several European countries. Kvaerner conducted a study in Norway of hospital admissions for AOM from 1999 to 2005 among children aged 7 years or younger. Hospitalization for AOM was less frequent, but the incidence of acute mastoiditis remained stable at approximately 6 per 100,000 children over time. The consultation rates to the general physicians in the Netherlands for otitis media during 1995 to 2003 in children from birth to 13 years of age were assessed using the research database of the Netherlands University Medical Center Utrecht Primary Care Network. The overall consultation rates decreased by 9% for AOM and 34% for OME. In children aged 2 to 6 years and those aged 6 to 13 years, the rate of AOM declined by 15% and 40%, respectively; the rates of OME declined by 41% and 48%, respectively. In children younger than 2 years of age, however, the rates of AOM and OME increased by 46% and 66%.
Data from the General Practitioner Database in the United Kingdom were analyzed for events classified as AOM or “glue ear” in the years 1991 to 2001. Total consultations for AOM and glue ear in children aged 2 to 13 years had changed from 105.3 to 34.7 and 15.2 to 16.7 per 1000 per year, respectively. However, studies from developing countries and indigenous populations continue to demonstrate a heavy burden of OM, particularly chronic suppurative OM.
Further surveillance is needed. As noted previously, disease rates must continue to be monitored to determine the effects of vaccines and changes in treatment on the epidemiology of otitis media.
Risk factors may be host related (age, gender, race, prematurity, allergy, immunocompetence, cleft palate and craniofacial abnormalities, genetic predisposition) as well as environmental (URIs, seasonality, day care, siblings, tobacco smoke exposure, breastfeeding, socioeconomic status, pacifier use, and obesity) and are considered important in the occurrence, recurrence, and persistence of middle ear disease.
The highest incidence of AOM is between 6 and 11 months of age, and onset of the first episode of AOM before 6 months or 12 months of age is a powerful predictor of recurrence. The risk of persistent MEE after an episode of AOM is inversely correlated with age, and children who experience their first episode of MEE before 2 months of age are at a higher risk for persistent fluid during their first year of life than are children who have their first episode later.
Most investigators have reported no apparent sex-based difference in the incidence of OME. Paradise and coworkers, in a study involving more than 2000 infants, found males had more time with MEE, although the difference was not large. Some but not all studies have found a significantly higher incidence of AOM in males as well as more recurrent episodes than in females.
Earlier studies have suggested a lower incidence of otitis media in African-American children than in white children. More recent studies in which the children were followed prospectively from infancy to age 2 years with routine examinations of the ears every 6 weeks showed no difference between the African-American and white children in their experience with otitis media. A third study, part of an American population-based sample survey evaluating school children 6 to 10 years of age with tympanometry, reported no difference between African-American and white children; the prevalence of OME was significantly higher in Hispanic children compared with white children. However, recent surveys have shown that non-Hispanic whites have the highest OM rates for all ages. Data collected from 1997 to 2006 to assess demographic disparity among children with recurrent episodes of AOM (three or more episodes reported by parents during the past 12 months) reported an average annual recurrent OM prevalence in children younger than 18 years (mean age, 8.6 years) of 6.6% over the 10-year period. Recurrent episodes occurred more often in children who were white (7.0%). Multivariate analysis showed that black Hispanic and other racial groups were less likely to have recurrent OM than white children, possibly due to less access to care, resulting in underdiagnosed episodes of OM.
Some studies have shown a possible association between low birth weight and prematurity and otitis media, but others have not. In many of these studies, however, the sample sizes have been relatively small. In the Norwegian Mother and Child Cohort, an analysis of 33,192 children born between 1999 and 2005 showed that preterm birth but not low birth weight was modestly associated with single and recurrent AOM in the first 18 months of life. In a prospective cohort study of 136 children treated with tympanostomy tubes, a positive but nonsignificant association was documented between low birth weight or low gestational age or history of incubator care and recurrent OME.
There is still controversy regarding the role of allergy in the pathogenesis of otitis media. Allergy is a common problem in children, occurring at a time when respiratory infections and otitis media are common. Most, but not all, epidemiologic studies have supported an association. The cited studies generally found a higher frequency of OME in allergic children than in age-matched nonallergic children, as well as higher frequencies of allergy in children with OME than in children without OME.
Children with recurrent otitis media as well as other recurrent infections may have a defect in the immune system such as a defect in phagocyte function, humoral immunity, local immunity, or other immune defects. Children infected with the human immunodeficiency virus demonstrate a significantly higher recurrence rate than normal children or children who have seroconverted. Whereas agammaglobulinemia and hypogammaglobulinemia are uncommon, deficient or lowered Ig A or decreased levels of one or more IgG subclasses, particularly IgG2, are more common. A recent study found that young otitis-prone children mounted less of an antibody response to five pneumococcal proteins after nasopharyngeal colonization or AOM than did non–otitis-prone children.
Cleft Palate/Craniofacial Abnormality.
Otitis media is considered “universal” in infants younger than 2 years of age with unrepaired cleft palate. After surgical repair of the palate, the occurrence of otitis media is reduced, probably because of improvement in eustachian tube function. However, many children continue to have problems up into the teenage years. Newer palatal repair procedures may result in further reduction of middle ear disease. Otitis media also is common in children with other craniofacial abnormalities or Down syndrome, also due to anatomic or functional eustachian tube abnormalities. In children with Down syndrome, low resistance of the tube, in addition to poor active eustachian tube function, predisposes them to reflux of nasal secretions into the middle ear.
The frequency of occurrence of one episode of otitis media is so high that a genetic predisposition is highly unlikely. However, a predisposition to recurrent episodes of otitis media and chronic MEE may have a significant genetic component. The etiology of otitis media is multifactorial, involving environmental as well as genetic factors. A large number of genes may be involved, each contributing to a particular increase in disease risk.
Twin and triplet studies have been used to assess the heritability of otitis media. One retrospective study and one prospective study have demonstrated a strong heritability estimate for OM ranging from 0.74 to 0.79 in females and 0.45 to 0.64 in males. Heritability is a population statistic used to ascertain if a trait is heritable, and linkage and association studies may identify genetic regions or specific genes influencing the particular trait or disease. Two linkage studies have been performed. Daly and coworkers, using genome-wide linkage analysis, have suggested that chromosomal regions on 19q and 10q contain genes contributing to the susceptibility to chronic OME or recurrent AOM. Subsequent fine mapping of both regions further strengthened the evidence for this linkage. The second genome-wide linkage study demonstrated linkage regions with possible candidate genes on 17q12 ( AP2B1 , CCL5 , and a cluster of other CCL genes) and on 10q22.3 ( SFTPA2 ). Polymorphisms in genes encoding mannose-binding protein, surfactant protein, mucin expression, and cytokines have been associated with disease. Rye and colleagues have reported an association between polymorphisms in FBXO11 , the human homologue of a mouse model gene for chronic otitis media, and chronic OME/recurrent AOM in two Australian cohorts.
A study was conducted to assess the variation in environmental risk factors for otitis media across Western countries, including European countries, the United States, Canada, and Australia. The main risk factors for otitis media were day-care attendance, number of siblings, tobacco smoke exposure, breastfeeding, birth weight, socioeconomic status, and air pollution. However, the results indicated large variations in rates across the various countries: day care at ages 1 to 3 years: Sweden 75% versus Italy 6%; breastfed at 6 months: Norway 80% versus Poland 6%; and women smoking: Germany, France, and Norway 30% to 40% versus Portugal less than 10%.
Upper Respiratory Infection/Seasonality.
Both epidemiologic evidence and clinical experience strongly suggest that otitis media frequently is a complication of URI. The incidence of AOM is highest during the fall and winter months and lowest during spring and summer months, which parallels the incidence of URI. This correlation supports the hypothesis that an episode of URI plays an important role in the etiology of otitis media. Rhinovirus, RSV, adenovirus, and coronavirus have been detected in MEE during episodes of AOM. Upper respiratory tract infections with RSV, influenzavirus, and adenovirus often precede an episode of AOM. In a prospective study of Finnish children, 54% of ensuing AOM episodes were diagnosed by day 4 after the onset of URI symptoms. Winter and colleagues reported that an episode of OM was found in 33% of a cohort of closely monitored children with a cold-like illness.
Day Care/Home Care/Siblings.
Almost universally, day-care center attendance remains a very important risk factor for development of otitis media. For example, the prevalence of high negative middle ear pressure and flat tympanograms (type B), indicative of MEE, has been shown to be highest in children cared for in day-care centers with many children, intermediate in children in family day care with fewer children, and lowest in children cared for at home. Children attending day-care centers also have been shown to be more likely to have tympanostomy tubes inserted than children cared for at home.
Birth order has been shown to be associated with episodes of otitis media and percentage of time with MEE. First-born children had a lower rate of episodes of AOM and less time with MEE during the first 2 years of life than children with older siblings. Also, having more than one sibling was significantly related to early onset of otitis media.
The increased morbidity among children in day-care centers and in children with older siblings may be related to the greater opportunity for exposure to viral URI, which may cause eustachian tube dysfunction, leading to the development of otitis media.
Tobacco Smoke Exposure.
An association between otitis media and passive exposure to smoking has been reported by many investigators, whereas others have not demonstrated such an association. In most studies the information regarding smoke exposure has been obtained from the parents. A few recent studies have been able to more accurately determine the association between otitis media and smoke exposure by measuring cotinine, a metabolite of nicotine, in blood, urine, or saliva of the child. More information about the pathogenesis and duration and intensity of exposure is needed to clarify this association. Two recent studies have shown an association between middle ear status and parental smoking. In children exposed to parental smoking, tympanostomy tubes stayed in place for 59 weeks, compared with 86 weeks in children who were not exposed to smoking. Also, myringosclerosis was more prevalent in children with two smoking parents compared with those with no smoking parents (64% vs. 20%), and maternal smoking was associated with a highly increased risk of recurrent otitis media after insertion of tympanostomy tubes.
Currently, most national and international authorities, including the American Academy of Pediatrics and the American Academy of Family Physicians, the World Health Organization, and the United Nations Children’s Fund, recommend 6 months of exclusive breastfeeding. In 2004, Kramer and Kakuma published a comprehensive review of the world literature to determine health benefits of exclusive breastfeeding for 6 months compared with 3 to 4 months. They reported a decrease in the risk for gastrointestinal infection even in developed areas. It had not been shown previously that exclusive breastfeeding for 6 months or longer compared with 4 to less than 6 months in the United States provided greater protection against respiratory infections. Therefore, a secondary analysis of data from the National Health and Nutrition Examination Survey III, a population-based cross-sectional home survey conducted from 1988 to 1994, was undertaken. After adjustment for demographic variables, child care, and smoke exposure, the data revealed a statistically significant increased risk for both pneumonia (odds ratio [OR]: 4.27; 95% confidence interval [CI], 1.27-14.35) and three or more episodes of otitis media (OR: 1.95; 95% CI: 1.06-3.59) in those children breastfed 4 to less than 6 months. These findings further support the current recommendations that infants receive breast milk exclusively during the first 6 months of life.
Socioeconomic status and access to health care are factors that may affect the incidence of otitis media. It has been generally thought that otitis media is more common among persons in the lower socioeconomic strata as a result of poor sanitary conditions and crowding. Paradise and colleagues followed 2253 infants for 2 years in the United States and found an inverse relationship between the cumulative proportion of days with MEE and socioeconomic status. Data collected from 1997 to 2006 to assess demographic disparity among children with recurrent episodes of AOM (three or more episodes reported by parents during the past 12 months) reported that children living below the poverty level were at increased risk for recurrent OM (8%). It was also reported that OM was less often diagnosed in children who were uninsured (5.4%). Those with insurance had a slightly higher rate of recurrent OM (6.4%), probably because they had better access to care.
Niemelä and associates reported that pacifier use increased the annual incidence of AOM and calculated that pacifier use was responsible for 25% of AOM episodes in children younger than 3 years. They reported the results of an intervention trial in which parents in various well-baby clinics were taught that pacifier use was harmful and should be limited and parents in other clinics were not provided with this information. This led to a 29% decrease in AOM in the group provided with pacifier information. Pacifier use has been theorized to contribute to the development of otitis media, possibly due to the sucking action of the child propelling nasopharyngeal secretions into the middle ear or by the pacifier acting as a fomite. However, Brook and Gober cultured the surface of pacifiers from children with AOM but found no pathogens typical of AOM. The role of pacifier use in AOM remains unclear.
Recent studies have indicated a possible association between otitis media and obesity. Tympanostomy tube insertion and overweight were studied in a cohort of predominantly white children followed from birth to 2 years of age. Weight-for-length was calculated using well-child visit data. They found a significant relationship between tympanostomy tubes and weight at or above the ninety-fifth and eighty-fifth percentiles in 2-year-olds. In another cohort of children in Nova Scotia, overweight and obese children 10 to 11 years of age had more health care provider contacts for OM and were more likely to have recurrent OM than normal-weight children.
Prevention of Disease
Prevention and modification of risk factors and vaccine development are two recommended strategies for the prevention of disease.
Management of Environmental Factors
Promotion of breastfeeding in the first 6 months of life, avoidance of supine bottle feeding and pacifier use, and elimination of passive tobacco smoke may be helpful in reducing the risk of development of otitis media. Alteration of child care arrangements so that the child is exposed to fewer children may also be of benefit.
The three most common bacteria isolated from the middle ear are S. pneumoniae , H. influenzae , and M. catarrhalis . At present, the S. pneumoniae vaccines (Pneumovax and Prevnar 13) are the only bacterial vaccines available for otitis media. Although respiratory viruses, such as RSV, influenzavirus, adenovirus, parainfluenza virus, and rhinovirus, have been isolated in MEE using PCR, influenza vaccine is the only available recommended viral vaccine today that may have an impact on otitis media.
Streptococcus pneumoniae Vaccine.
Pneumovax is a 23-valent polysaccharide vaccine that is not efficacious in children 2 years of age or younger because of poor antigen production in this age group. Prevnar is a conjugated vaccine in which pneumococcal polysaccharides are conjugated to a nontoxic mutant of diphtheria toxin. The 7-valent vaccine (Prevnar, PCV7), which included serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was licensed for use in the United States in 2000 and recommended for use in children younger than 6 years of age by the American Academy of Pediatrics. This was replaced in 2010 in the United States by Prevnar 13, which included the serotypes in PCV7 with the addition of the serotypes 1, 3, 5, 6A, 7F, and 19A. PCV13 is recommended for all children 2 to 59 months of age, as well as for children 60 to 71 months of age with increased susceptibility to pneumococcal disease. Children up to 59 months of age who received four doses of PCV7 should receive one dose of PCV13. The vaccine is also licensed for use in adults 50 years and older, but at present the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends its use specifically in immunocompromised adults 19 years of age and older as well as those with cerebrospinal fluid (CSF) leaks or cochlear implants.
The efficacy for AOM of the 7-valent vaccine was evaluated in several randomized clinical trials. The trial from Northern California Kaiser Permanente enrolled 37,868 children, randomly assigned them to either pneumococcal conjugate vaccine or a meningococcal type C conjugate vaccine, and followed them prospectively; an overall reduction of episodes of otitis media of 7% was reported. However, children with recurrent otitis media benefited from the vaccine with a reduction in otitis media episodes ranging from 9.3% to 22.8%, increasing as the frequency of episodes of AOM increased. In addition, immunized children were 20.1% less likely to require tube placement than control subjects. The PCV7 vaccine demonstrated a much higher efficacy (>80%) in reducing invasive pneumococcal disease than in reducing the burden of otitis media. Additional follow-up of the study subjects continued to demonstrate a modest amount of protection against episodes of AOM and need for tympanostomy tube insertion. In a Finnish study of 1662 children randomized to receive either PCV7 vaccine or a hepatitis B vaccine, with follow-up to the age of 24 months, a bacterial diagnosis was made based on a culture of the middle ear fluid, in addition to the clinical assessment of episodes of AOM. The vaccine reduced the number of AOM episodes from any cause by 6%, the number of culture-confirmed pneumococcal episodes by 34%, and the number of episodes due to the vaccine serotypes by 57%. The number of episodes attributed to serotypes that were cross-reactive with those in the vaccine was reduced by 51%, whereas the number of episodes due to all other serotypes increased by 33%. The modest response in reducing number of episodes of AOM was due to a decrease in vaccine efficacy against serotype-specific infections as well as an increase in AOM episodes due to nonvaccine serotypes. A second trial was conducted in Finland using a 7-valent pneumococcal polysaccharide–meningococcal outer membrane protein complex conjugate vaccine in 1666 children who were followed for 24 months. This trial showed no reduction in overall number of AOM episodes. The reduction in number of AOM episodes due to any culture-confirmed pneumococci was 25% and to vaccine serotype pneumococci, 56%—results similar to those with the PCV7. This vaccine failed to show protection against cross-reactive serotypes. An increased rate of carriage of nonvaccine serotypes was noted among infants vaccinated with the pneumococcal conjugate vaccine.
With use of the PCV7 vaccine, pneumococcal colonization in the nasopharynx changed as the vaccine caused a reduction in the carriage rate of vaccine serotypes and replacement with nonvaccine serotypes. It should be noted that a reduction in nasopharyngeal carriage of vaccine serotypes and an increase in nonvaccine serotypes was also seen in children younger than 7 months of age. With the introduction of PCV13, decreased nasopharyngeal carriage of all S. pneumoniae strains as well as the strains not contained in PCV7 was shown in a French study comparing children who received only PCV7 with those receiving PCV13. Whether this will mean fewer cases of OM will only be revealed as monitoring of OM cultures continues.
In the United States and Finland, the initial immunization with PCV7 and now PCV13 is at age 2 months based on the results from the clinical trials. However, the question of whether or not the results obtained in the Finnish and U.S. trials could be extrapolated to older children who already had a history of recurrent episodes of AOM was addressed by Dutch and Belgian trials. Seventy-eight and 383 children with documented histories of recurrent AOM were enrolled in the Belgian and Dutch studies, respectively. In both trials, children between the ages of 1 and 7 years were immunized at entry with PCV7 followed by a booster immunization with a 23-valent pneumococcal polysaccharide vaccine 7 months later. Children were followed for a total of 18 months in the Dutch trial and 26 months in the Belgian trial. The results from these two studies did not lend any support to the use of pneumococcal conjugate vaccine to prevent AOM in previously unvaccinated toddlers and children with a history of recurrent AOM. The differences in outcome between the studies in older children and those in healthy infants may be caused by differences in age at immunization. In the infant studies, the PCV7 immunization may prevent or delay nasopharyngeal colonization of the most frequent pneumococcal serotypes and consequently delay pneumococcal episodes of AOM until a later age. In older children, who already are carriers of pneumococci, there is rapid replacement of pneumococcal vaccine serotypes with nonvaccine serotypes.
Infants immunized with PCV13 are unlikely to elicit protective serum antibody concentrations during the first 4 to 6 months of life, when recurrent AOM begins. Maternal immunization with pneumococcal vaccine is another approach that is currently being studied in animals as well as in humans. A randomized clinical trial was conducted to evaluate the immunogenicity and reactogenicity of the 23-valent pneumococcal polysaccharide vaccine among pregnant women in the Philippines. A significant rise in antibody to polysaccharides varying from 3.3- to 9.1-fold for individual serotypes before and after vaccination was seen in the immunized mothers relative to that in the control subjects. The level of polysaccharide-specific antibody in cord blood was also significantly higher in the immunized group, indicating transfer from mother to infant to provide enhanced protection. Adverse reactions were mild and required no treatment. Healy and Baker, reviewing the subject of maternal vaccination, found strong evidence that maternal immunization would be a feasible approach, particularly for providing early protection to children at high risk. The main concerns with maternal immunization appear to be the fear of risk of birth defects.
Haemophilus influenzae Vaccine.
Because nontypeable H. influenzae is one of the most common bacterial pathogens isolated from middle ear fluid in AOM, much effort has been channeled into developing an effective vaccine. Many different approaches using animal models have been used to develop vaccine antigens for nontypeable H. influenzae –induced otitis media, including the following proteins: outer membrane protein P5, 26, P2, P6, Htr protein, protein D, phosphorylcholine, detoxified lipooligosaccharides, and type 1V Pili. For the first time, however, it was possible to demonstrate an effective H. influenzae antigen for otitis media in a clinical trial using an 11-valent vaccine with the pneumococcal capsular polysaccharides conjugated to protein D, an outer membrane protein of H. influenzae . However, a trial of 10-valent pneumococcal nontypeable H. influenzae protein D-conjugate vaccine found no efficacy for nasopharyngeal colonization with H. influenzae .
Moraxella catarrhalis Vaccine.
Moraxella catarrhalis is considered the third most common bacterial pathogen isolated from the middle ear. Although the frequency of M. catarrhalis infections has previously been rather modest, recent studies have indicated that the frequency of nasopharyngeal colonization with M. catarrhalis in children with otitis media increased with the widespread use of the pneumococcal conjugate vaccine. Therefore, for the greatest impact on reducing otitis media episodes, the development of a vaccine that contains M. catarrhalis as well as S. pneumoniae and H. influenzae antigens is necessary. Very little progress has been made in defining the protective immune response in M. catarrhalis . However, protective immune responses to M. catarrhalis in adults with chronic obstructive pulmonary disease have been identified. Candidate M. catarrhalis vaccine antigens that have been shown to induce potentially protective responses include outer membrane protein OlpA, CopB, filamentous hemagglutinin (FHA-like protein), and lipooligosaccharides.
Based on evidence regarding the role of viruses in the pathogenesis of AOM, the development of viral vaccines should be strongly promoted. It should be recognized that bacterial vaccines only prevent the bacterial complications of a viral infection, whereas viral vaccines act at an earlier stage in the pathogenesis of AOM. Thus, viral vaccines have the potential to prevent viral URIs, thereby potentially preventing the development of AOM as a complication of bacterial colonization of the nasopharynx.
The only commercially available viral vaccine today used for prevention of otitis media is the influenza vaccine, which is recommended for all children 6 months of age and older by the American Academy of Pediatrics. Currently, two types of influenza vaccine are available for children. Trivalent inactivated influenza vaccine (TIV) contains killed viruses and is given intramuscularly to children 6 months and older and adults. Live-attenuated influenza vaccine (LAIV) contains live virus, is given intranasally, and currently is licensed by the U.S. Food and Drug Administration (FDA) for healthy persons 2 through 49 years of age. A study in children 6 to 59 months of age compared intranasal LAIV to intramuscular TIV. The LAIV was overall superior to the inactivated vaccine in preventing influenza episodes (54.9% fewer cases of culture-confirmed influenza episodes in the LAIV group, P <.001), but rates of wheezing and hospitalization were higher in the youngest children who received the LAIV vaccine. Currently, for children younger than 6 months who are too young to receive either of the approved vaccines, it is recommended that close contacts be immunized. The efficacy of maternal vaccination during pregnancy for preventing influenza in their young infants is still unsettled; the U.S. Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists have recommended influenza immunization for all pregnant women in any trimester since 2004, but only 10% to 40% of pregnant women are immunized. A study is ongoing to look at the efficacy of maternal influenza vaccination.
A prospective study of respiratory infections in children 13 years or younger was conducted during two respiratory seasons in Finland. The average annual rate of influenza was highest (179 cases per 1000 children) among children younger than 3 years of age. AOM developed as a complication of influenza in 39.7% of children younger than 3 years. For every 100 influenza-infected children younger than 3 years, there were 195 days of parental loss of work (mean, 3.2 days). The investigators concluded that vaccination of children younger than 3 years of age may be beneficial for reducing the direct and indirect costs of childhood AOM.
Several clinical trials have addressed the efficacy of inactivated influenza vaccine in preventing otitis media. Hoberman and coworkers conducted a randomized double-blind, placebo-controlled 2-year clinical trial in 786 children 6 to 24 months of age in Pittsburgh, Pennsylvania. The investigators did not identify any significant reduction in the burden of AOM from administration of inactivated trivalent influenza vaccine (TIV). However, in the first year of the study, the efficacy of the vaccine against culture-confirmed influenza was 66%, whereas in the second year of the study the efficacy was −7%. The low efficacy rate in the second year may be explained by the fact that the attack rate of influenzavirus in the second year did not reach epidemic proportions, in contrast with the first year (3.3% vs. 15.9% in the placebo group). Another study was single-blinded and evaluated the efficacy of inactivated influenza vaccine in preventing otitis media in 119 children 6 to 60 months of age attending day care in Turkey. Efficacy rates for the vaccine against AOM, OME, and otitis media were 51%, 18%, and 18%, respectively. A prospective single-blinded placebo-controlled study of TIV in 180 children 1 to 5 years of age with a history of recurrent AOM found reduced rates of AOM in children who received vaccine (mean number of AOM episodes, 0.94 vs. 2.08; P = .03).
Respiratory Syncytial Virus Vaccine.
The seriousness of RSV infection in infants and children and the need for an RSV vaccine are widely recognized. In addition to causing lower airway infections, RSV is one of the major viruses contributing to the development of AOM. Live attenuated vaccines have been investigated, but as yet there is no vaccine that produces safe, long-lasting immunity to RSV. A phase I study in adults of an RSV fusion protein nanoparticle vaccine was recently reported to have promising results. However, at present, prophylaxis with pavilizumab, a costly monoclonal antibody, is recommended to prevent RSV lung disease in high-risk infants.
An alternative approach to preventing RSV infection is maternal immunization. Munoz and colleagues conducted a study to assess safety and immunogenicity of an RSV purified fusion protein 2 subunit vaccine in 35 pregnant women in their third trimester and the effect on the offspring. The infants were followed during their first RSV season. Seventy-five percent of the immunized infants had a response to the purified fusion protein 2 by Western blot analysis, compared with none of the control subjects. The transplacental transfer of vaccine-induced maternal antibodies was efficient, and no increase in frequency or severity of respiratory tract infections was observed in the immunized infants. The infants were born healthy, and no adverse events related to maternal immunization were documented. Stensaballe and colleagues reported that infants younger than 6 months of age with high levels of RSV neutralizing antibody from their mothers had fewer hospitalizations for RSV; at present, maternal immunization is not universally recommended.