PEDIATRICS Vol. 119 No. 4 April 2007, pp. 707-715 (doi:10.1542/peds.2006-2138)
ARTICLE |
Reduction of Frequent Otitis Media and Pressure-Equalizing Tube Insertions in Children After Introduction of Pneumococcal Conjugate Vaccine
a Departments of Pediatrics
c Preventive Medicine
e Biostatistics
f Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
b Department of Pediatrics and Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York
d National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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ABSTRACT |
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 TOP ABSTRACT PATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. Streptococcus pneumoniae is an important cause of otitis media in children. In this study we estimated the effect of routine childhood immunization with heptavalent pneumococcal conjugate vaccine on frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and pressure-equalizing tube insertions.
PATIENTS AND METHODS. The study population included all children who were enrolled at birth in TennCare or selected upstate New York commercial insurance plans as of July 1998 and continuously followed until 5 years old, loss of health plan enrollment, study outcome, or end of the study. We compared the risk of developing frequent otitis media or having pressure-equalizing tube insertion for 4 birth cohorts (1998–1999, 1999–2000, 2000–2001, and 2001–2002) by using Cox regression analysis. We used data from the National Immunization Survey to estimate the heptavalent pneumococcal conjugate vaccine uptake for children in these 4 birth cohorts in Tennessee and New York.
RESULTS. The proportion of children in Tennessee and New York who received at least 3 doses of heptavalent pneumococcal conjugate vaccine by 2 years of age increased from 
1% for the 1998–1999 birth cohort to 
75% for the 2000–2001 birth cohort. By age 2 years, 29% of Tennessee and New York children born in 2000–2001 had developed frequent otitis media, and 6% of each of these birth cohorts had pressure-equalizing tubes inserted. Comparing the 2000–2001 birth cohort to the 1998–1999 birth cohort, frequent otitis media declined by 17% and 28%, and pressure-equalizing tube insertions declined by 16% and 23% for Tennessee and New York children, respectively. For the 2000–2001 to the 2001–2002 birth cohort, frequent otitis media and pressure-equalizing tubes remained stable in New York but increased in Tennessee.
CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, children were less likely to develop frequent otitis media or have pressure-equalizing tube insertions.
Key Words: otitis media • pressure-equalizing tubes • middle ear ventilation tubes • tympanostomy tubes • epidemiology • pneumococcal conjugate vaccine
Abbreviations: PCV7—heptavalent pneumococcal conjugate vaccine • PET—pressure-equalizing tube • ICD-9—International Classification of Diseases, Ninth Revision • NIS—National Immunization Survey
Streptococcus pneumoniae is an important cause of otitis media, a common childhood illness that has resulted in an estimated $5.3 billion annually in direct medical costs across the United States.1,2 The efficacy of 7-valent pneumococcal conjugate vaccine (PCV7) in reducing otitis media was evaluated in 2 randomized, controlled trials. The Finnish and Kaiser Permanente trials found that young children who received PCV7 had a 6% and 7.8% overall reduction in the prevalence of otitis media, respectively, but this decline was statistically significant only in the Kaiser study.3,4 The vaccine efficacy for prevention of pressure-equalizing tube (PET) insertions, the most common surgical procedure in children,5 was 23% by 3.5 years in the Kaiser trial and 39% by 4 to 5 years in the Finnish trial.4,6
Since PCV7 was incorporated into the routine immunization schedule in the United States by mid 2000,7,8 several studies have demonstrated a dramatic decrease in invasive pneumococcal disease.9,10 National survey data indicated that otitis media visits have decreased by 246 per 1000 children, a 20% decline with no compensatory increase in other respiratory visits.11 Our previous evaluation of children enrolled in Tennessee Medicaid and private insurance programs in the Rochester, New York, area showed declines in otitis media visits consistent with these national data.12 To date, there have been no evaluations of PCV7 program effectiveness by using longitudinal data from individual children to measure the change in risk of developing frequent otitis media or having PETs inserted.
In this study, we used an ecological analysis to determine the risk of frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and PET insertions among 4 birth cohorts (1998–1999, 1999–2000, 2000–2001, and 2001–2002). We hypothesized that the risk of frequent otitis media and PETs would decrease from the 1998–1999 birth cohort, in which few children received PCV7 doses, to subsequent birth cohorts who had progressively increasing PCV7 uptake.
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PATIENTS AND METHODS |
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TOPABSTRACTPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Sources of Data
TennCare is Tennessee's managed care program that includes the Medicaid population and other low-income children. Each enrollee selects from 1 of 7 managed care organizations. During the study period, it included 50% of children born in Tennessee and all state children who were enrolled in Medicaid, with a high proportion of children from racial and ethnic minority groups and low-income families. The upstate New York database contains data from 3 commercial insurance managed care organizations, which together provided coverage for nearly 70% of children in the Rochester, New York, region.
Because of incomplete PCV7 vaccination information in these administrative databases, data from the National Immunization Surveys conducted in 2001–2004 were used to estimate PCV7 vaccination coverage among children born between February 1998 and May 2003. This survey is designed to measure vaccination coverage in a nationally representative sample of US children aged 19 to 35 months. The National Immunization Survey used random-digit dialing to identify households with age-appropriate children and followed these telephone interviews with mailed surveys to the children's vaccination providers. Only provider-verified vaccination histories are included in the analysis.
Study Population
We identified children born between July 1 and June 30, 1998–1999, 1999–2000, 2000–2001, and 2001–2002, and enrolled within 30 days of birth in TennCare or in commercial insurance plans of upstate New York. These birth cohorts were continuously followed until age 5, loss of enrollment, death, study outcome, or end of the surveillance period (June 30, 2004). For each birth cohort, we estimated the cumulative proportion of children who developed frequent otitis media or had PETs inserted.
Birth cohorts were defined by using a July to June year for 2 reasons. Although PCV7 was licensed in the United States in February 2000, coverage of PCV7 by most health insurance companies did not begin at that time. The routine administration of PCV7 began in the summer of 2000, when the American Academy of Pediatrics and the Advisory Committee on Immunization Practices published recommendations and the Vaccines for Children Program began to cover PCV7.7,8,13 A survey of primary health care providers in Tennessee and upstate New York confirmed that routine administration of PCV7 began after the summer of 2000 in these regions.14 Another reason for a July to June year was that each year includes 1 winter respiratory virus season as compared with a calendar year, which may include 0, 1, or 2 winter respiratory viral seasons.
Institutional review boards of Vanderbilt University, the State of Tennessee, University of Rochester, and the Centers for Disease Control and Prevention approved this study.
Study Outcomes
We identified 2 outcomes in cohort children: development of frequent otitis media and PET insertions. We identified all hospitalizations, emergency department visits, and outpatient visits for otitis media by International Classification of Diseases, Ninth Revision (ICD-9) codes (ICD-9 381.0–381.4, 382.x). An episode of otitis media was the first such visit or a visit at least 21 days after a previous otitis media visit to distinguish reinfections from relapses or persistent infections.4,15,16 A child developed frequent otitis media on the date of the first of the following: the third episode of otitis media within 6 months or the fourth episode within 1 year.3 A child was determined to have PET insertions on the date of the first visit with this procedure code (Current Procedural Terminology, Fourth Edition, 69433 or 69436).
Statistical Analysis
For each birth cohort, we used the Kaplan-Meier estimator to determine the cumulative proportion of children who developed frequent otitis media or had PETs inserted according to age in days; this method adjusts for children who drop out of the cohorts before experiencing the outcomes of interest. In addition, we used Cox regression models to evaluate the association between birth cohort (1998–1999, 1999–2000, 2000–2001, and 2001–2002) and risk of developing frequent otitis media or having PET insertion from birth through 2 years of age. Birth cohort was analyzed as a categorical variable using the 1998–1999 cohort as the reference. Of children enrolled at birth, 24% of Tennessee children and 39% of New York children, respectively, dropped out by 2 years of age. Separate analyses of outcomes in the first year of life for children who did and did not drop out showed similar patterns, suggesting absence of informative censoring (data not shown). To verify that the criteria for PET insertions were similar across cohorts, we compared the age-specific proportion of children with PETs who met the study criteria for frequent otitis media at the time of surgery.
We used National Immunization Survey (NIS) data (2001–2004) from Tennessee and New York to estimate PCV7 vaccination coverage by 2 years of age in the 4 birth cohorts of interest.17 For each birth cohort, we combined the NIS survey years that sampled children with appropriate birthdays. Because 2 to 3 NIS survey years were used for each estimate of PCV7 coverage by 2 years, each estimate was adjusted by dividing the individual weights for the included surveys by the total number of surveys used.18 Coverage estimates and 95% confidence intervals were calculated for the subgroup of children in the birth cohort, accounting for the complex survey design.19
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RESULTS |
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TOPABSTRACTPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The demographics of the study populations are shown in Table 1. Each of the 4 birth cohorts from Tennessee accounted for 25% of the Tennessee population, whereas each birth cohort from New York accounted for 21% to 27% of the upstate New York population. The proportion of children who had either frequent otitis media or were continuously enrolled until 1 and 2 years of age was 77% and 63% in the TennCare population and 59% and 50% in the upstate New York private insurance population.
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Frequent Otitis Media
Tennessee
The TennCare population included 150122 children with an average of 37531 children per birth cohort. From the 1998–1999 through the 2001–2002 birth cohorts, 11007 (7%) and 38905 (26%) children lost enrollment during the first and second years of life, respectively. Overall, 39763 (26%) children had frequent otitis media by 2 years of age. The cumulative proportion with frequent otitis media by 2 years old was 33% among children born in 1998–1999 compared with 29%, 29%, and 31% for the subsequent 3 birth cohorts (Fig 1A). In comparison to the 1998–1999 birth cohort, the decrease in frequent otitis media was 16% for the 1999–2000 cohort, 17% for the 2000–2001 cohort, and 8% for the 2001–2002 birth cohort (Table 2 ). Exclusion of serous otitis codes (ICD-9 381.0–381.4) from the definition of otitis media in the Tennessee data resulted in a 3% decrease in frequent otitis media visits for all birth cohorts and no change in any of the hazard ratios.
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New York
The New York commercial insurance population included 26409 children with an average of 6602 per birth cohort. In the first 3 birth cohorts, 5457 (26%) and 2656 (21%) children lost enrollment during the first and second years of life, respectively. Overall, 6067 (32%) children had frequent otitis media by 2 years of age. The cumulative proportion with frequent otitis media by 2 years old was 38% among children born 1998–1999 compared with 33%, 29%, and 27% in the 3 subsequent birth cohorts (Fig 1B). In comparison to the 1998–1999 birth cohort, there was a progressive decline in frequent otitis media that ranged from 16% to 33% (Table 2).
PETs
Tennessee
PETs were inserted in 8223 children. Corresponding with the decline in frequent otitis media, the proportion of children with PETs by 2 years of age declined (Fig 2A) from 7.1% in the 1998–1999 birth cohort to 6.3% and 6.1% in 2 subsequent birth cohorts then increased back to 7.1% in the 2001–2002 birth cohort. This change in PET insertions (Table 2) from the 1998–1999 cohort represented a 12% and a 16% decline in the 1999–2000 and 2000–2001 birth cohorts but no change for the 2001–2002 birth cohort.
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Among the TennCare population, 78% of children at 1 year of age and 89% at 2 years of age had frequent otitis media before PET procedure, with no significant differences in these proportions in the 4 birth cohorts.
New York
PETs were inserted in 1121 children. The cumulative proportion with PET insertions by 2 years of age in each birth cohort declined (Fig 2B) from 7.1% in the 1998–1999 cohort to 6.3%, 5.5%, and 5.8% in subsequent cohorts. This change in PET insertions represented a 13% to 23% decline (Table 2).
Among the New York commercial insurance population, 93% of children at 1 year of age and 95% at 2 years of age had developed frequent otitis media by the time of PET procedure, with no trends in these proportions over time.
PCV7 Vaccination Coverage
According to the NIS data, the proportion of children receiving PCV7 by 2 years of age according to state and birth cohort increased over time (Fig 3). The proportion of children who received 3 doses of PCV7 by 2 years of age progressively increased for the 1998–1999 to the 2001–2002 cohorts from 0% in both states to 73% in Tennessee and 82% in New York. The proportion of children who received 4 doses of PCV7 by 2 years of age increased from 0% in both states to 35% in Tennessee and 53% in New York.
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DISCUSSION |
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TOPABSTRACTPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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For the 2000–2001 birth cohort, we found a 17% and 28% decline, respectively, in frequent otitis media among Tennessee and New York children since PCV7 was incorporated into the childhood immunization schedule. Similarly, PET procedures by 2 years of age declined 16% and 23% since PCV7 introduction. This ecologic approach is supported by NIS PCV7 coverage estimates indicating that few children in the 1998–1999 birth cohort received PCV7 doses whereas progressively more children in the subsequent birth cohorts received PCV7.17 Interestingly, frequent otitis media and PET procedures progressively decreased for all birth cohorts in New York and through the 2000–2001 cohort in Tennessee. For the 2001–2002 Tennessee birth cohort, frequent otitis media was less than the 1998–1999 cohort but higher than the 2000–2001 cohort whereas PET procedures were similar to the 1998–1999 cohort. Although others have reported efficacy of PCV7, to our knowledge, this study is the first to evaluate the development of frequent otitis media and PET procedures in defined populations after PCV7 was recommended.
The reduction in the proportion of children with frequent otitis media and PET procedures was more marked in the New York private insurance population than in the TennCare population. Several factors likely contributed to this difference. According to the NIS data, PCV7 uptake and the proportion fully vaccinated was higher among New York children than among Tennessee children. Recent studies suggest that mucosal antibody response rarely develops after the primary series but is often demonstrated at age 13 or 14 months after receiving the booster dose, suggesting its importance for local mucosal immunity and, consequently, protection against otitis media.20 These children may have different rates of exposure to known risk factors, such as day care attendance and passive smoke exposure, which we did not measure. There may also be geographical differences among physicians as to what criteria they use to diagnose otitis media. Previous studies have found that children were more likely to have had PET procedures if they were from the South than the Northeast, were in day care, had no gaps in health coverage, or were of non-Hispanic white race and ethnicity.21 Furthermore, a higher proportion of New York than Tennessee children at each age group met criteria for frequent otitis media at the time of PET insertions, suggesting that the criteria for PET insertions may have been more stringent in the New York population.
The increase in frequent otitis media and PET insertions in the 2001–2002 birth cohort in Tennessee as compared with the 2 previous birth cohorts is a surprising and potentially important observation because the 2001–2002 cohort represents children with high PCV7 vaccination rates. It may reflect one or a combination of many factors. The increase in laboratory-confirmed pneumococcal disease from nonvaccine serotypes from the pre-PCV7 to post-PCV7 era has been reported for invasive disease and in one study on otitis media.22–26 Temporal changes in the children who are enrolled and disenrolled from insurance plans may have contributed to this discrepancy. Overall medical care utilization may have increased, which may obscure the vaccine effect. An increase in medical care utilization could increase visit rates for otitis media even if disease rates remained stable or decreased.
The incidence of PET insertions in our study populations is comparable to those reported for other populations. In a large, rural Kentucky practice, 2.0% to 2.2% of children received PETs by 1 year of age and 4.0 to 5.8% received PETs during the second year of life.27 Similarly, Paradise et al28 reported 1.8% and 4.2% of children had PETs placed during the first and second years of life, respectively. Our cumulative frequency of PETs for the 1998–1999 birth cohorts was 2.5% by 1 year of age and 7% by 2 years of age. Our 16% and 23% reduction in PETs in Tennessee and New York is comparable to the 20% decline reported in the Kaiser Permanente trial.29
Our results should be interpreted in light of some potential limitations. In this ecologic study, we cannot exclude the possibility that other concurrent factors, such as the encouragement of the judicious use of antibiotics, may have influenced physicians' diagnostic patterns for otitis media.30 Furthermore, administrative data claims incompletely capture individual vaccinations and the PCV7 status of the study population is not known. However, national estimates show an increase in full PCV7 vaccination by 2 years of age from 2001–2002 to 2003–2004.17 Because few children in the 1998–1999 were vaccinated whereas most were vaccinated in the 2001–2002 cohort, we cannot compare those who did and did not receive PCV7 within each cohort. Even if feasible, comparing children who are or are not vaccinated is problematic because children who receive vaccinations are more likely to seek care and thus may be more likely to have otitis media diagnosed. In addition, it is possible that unvaccinated children indirectly benefited because of lower pneumococcal carriage rates and decreased transmission of vaccine serotypes with implementation of PCV7 vaccination in the populations.31–33
Study results were limited to the children who qualified for TennCare and upstate New York commercial insurance. Because the eligibility criteria for Medicaid vary by state and over time, Tennessee results may not be representative of all Medicaid populations. The microbiology of otitis media and the proportion attributable to S pneumoniae cannot be ascertained from this study. However, our results are compatible with findings through 2003 that the microbiology of acute otitis media has changed since the introduction of PCV7 with 35% reduction in the prevalence of S pneumoniae isolates among bacteria causing otitis media and minimal replacement with nonvaccine pneumococcal serotype isolates.34,35
We found a greater decline in frequent otitis media for the 2000–2001 birth cohort, 17% and 28% in Tennessee and New York, than the 9.3% decline in the Kaiser Permanente trial.29 The cumulative proportion of children with frequent otitis media in the 1998–1999 birth cohort was slightly higher (33% in Tennessee and 36% in New York) than in previous studies. In the Kaiser trial, 28% of control children had frequent otitis media (3 episodes within 6 months) by 3.5 years of age.29 In other populations, 17.3% of Boston children had 3 episodes of otitis media in their first year of life,16 and 28% to 31% of rural Kentucky children had 4 or more episodes of otitis media by age 1 year.27 Our definition of otitis media included the code for serous otitis media, which may account for our modestly higher estimates.36 In Tennessee, we found that the proportion with frequent otitis media decreased by 3% when serous otitis media was excluded and that the hazard ratios were not impacted. Another possible explanation for the greater reduction in frequent otitis media than that seen in clinical trials is that there could be both direct and indirect benefits of PCV7 for partially vaccinated and nonvaccinated children.31–33 From 2001 to 2004, there was a significant decline in nasopharyngeal carriage for vaccine-serotype pneumococcus among healthy children <7 years of age who resided in a state with high PCV7 coverage.37 In contrast, no change in nasopharyngeal carriage of vaccine-serotype pneumococcus was found among children 2 to 5 years of age who had participated in a PCV7 trial but lived in a largely unvaccinated community.38
Estimating PCV7 coverage for the study birth cohorts has some limitations. Because the NIS is designed to provide data on nationally representative coverage, estimates for individual states should be interpreted with caution because they are less precise than national estimates.39 In addition, the survey weights were not originally designed for analysis by birth cohort but were adjusted by using a standard statistical technique.18 Finally, as in any survey, incomplete reporting may have resulted in an underestimate of coverage. However, this rapid rise of PCV7 coverage in the survey for New York correlated well and at the same time period noted by a community-wide random sample of medical charts in the Rochester, New York area, the same geographic area as this study.40
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CONCLUSIONS |
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TOPABSTRACTPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The declines in frequent otitis media and PET insertions matched or exceeded the results in randomized, controlled trials, suggesting direct and indirect benefits to children who were or were not fully vaccinated. These findings are particularly encouraging in light of PCV7 shortages. Furthermore, these reductions in frequent otitis media and PETs are higher than that seen in randomized, controlled trials and may have important implications on the cost-effectiveness analyses for PCV7. However, whether these findings continue or wane, as suggested by the 2001–2002 birth cohort from New York and Tennessee, respectively, is important and deserves additional study and monitoring.
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ACKNOWLEDGMENTS |
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This project was supported by cooperative agreement U38/CCU417958 from the Centers for Disease Control and Prevention (CDC) and U50/CCU30086, TS-0825 from American Teachers of Preventive Medicine/CDC. Dr Poehling also received support from K23 AI065805 (National Institute of Allergy and Infectious Diseases, National Institutes of Health) and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.
Data to conduct the study were obtained from the Tennessee Department of Health and the TennCare Bureau.
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FOOTNOTES |
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Accepted Dec 12, 2006.
Address correspondence to Katherine A. Poehling, MD, MPH, Department of Pediatrics, Wake Forest University Medical Center, Medical Center Blvd, Winston-Salem, NC 27157. E-mail: kpoehlin{at}wfubmc.edu
The views in this article are the sole responsibility of the authors and do not necessarily represent the official views of the Centers of Disease Control and Prevention.
Dr Poehling's current affiliation is Department of Pediatrics, Wake Forest University Medical Center, Winston-Salem, NC.
The authors have indicated they have no financial relationships related to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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 M. A. O'Brien, L. A. Prosser, J. L. Paradise, G. T. Ray, M. Kulldorff, M. Kurs-Lasky, V. L. Hinrichsen, J. Mehta, D. K. Colborn, and T. A. Lieu New Vaccines Against Otitis Media: Projected Benefits and Cost-effectiveness Pediatrics, June 1, 2009; 123(6): 1452 - 1463. [Abstract] [Full Text] [PDF]
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 S. J. Alter Pneumococcal Infections Pediatr. Rev., May 1, 2009; 30(5): 155 - 164. [Full Text] [PDF]
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 M. E. Pichichero, J. R. Casey, A. Hoberman, and R. Schwartz Pathogens Causing Recurrent and Difficult-to-Treat Acute Otitis Media, 2003-2006 Clinical Pediatrics, November 1, 2008; 47(9): 901 - 906. [Abstract] [PDF]
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J. Ongkasuwan, T. A. Valdez, K. G. Hulten, E. O. Mason Jr, and S. L. Kaplan Pneumococcal Mastoiditis in Children and the Emergence of Multidrug-Resistant Serotype 19A Isolates Pediatrics, July 1, 2008; 122(1): 34 - 39. [Abstract] [Full Text] [PDF]
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S. B. Meropol Valuing Reduced Antibiotic Use for Pediatric Acute Otitis Media Pediatrics, April 1, 2008; 121(4): 669 - 673. [Abstract] [Full Text] [PDF]
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C. M. Sox, J. A. Finkelstein, R. Yin, K. Kleinman, and T. A. Lieu Trends in Otitis Media Treatment Failure and Relapse Pediatrics, April 1, 2008; 121(4): 674 - 679. [Abstract] [Full Text] [PDF]
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Invasive Pneumococcal Disease in Children 5 Years After Conjugate Vaccine Introduction--Eight States, 1998-2005 JAMA, March 19, 2008; 299(11): 1253 - 1255. [Full Text] [PDF]
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F. Zhou, A. Shefer, Y. Kong, and J. P. Nuorti Trends in Acute Otitis Media-Related Health Care Utilization by Privately Insured Young Children in the United States, 1997-2004 Pediatrics, February 1, 2008; 121(2): 253 - 260. [Abstract] [Full Text] [PDF]
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 D. Schiff Multiresistant Pneumococci in Otitis Media AAP Grand Rounds, January 1, 2008; 19(1): 4 - 4. [Full Text] [PDF]
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M. E. Pichichero and J. R. Casey Emergence of a Multiresistant Serotype 19A Pneumococcal Strain Not Included in the 7-Valent Conjugate Vaccine as an Otopathogen in Children JAMA, October 17, 2007; 298(15): 1772 - 1778. [Abstract] [Full Text] [PDF]
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 C. Kemp PCV7 vaccine associated with decrease in OM AAP News, June 1, 2007; 28(6): 2 - 2. [Full Text] [PDF]
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