Skip Navigation

Acute Otitis Media Caused by Moraxella catarrhalis: Epidemiologic and Clinical Characteristics

  1. Arnon Broides1,2,*,
  2. Ron Dagan3,
  3. David Greenberg3,
  4. Noga Givon-Lavi3, and
  5. Eugene Leibovitz2,3
  1. 1Pediatric Immunology Clinic, Beer-Sheva, Israel
  2. 2Pediatric Emergency Department, Beer-Sheva, Israel
  3. 3Pediatric Infectious Disease Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  1. Reprints or correspondence: Dr Arnon Broides, Pediatric Emergency Department, Ben-Gurion University of the Negev, Soroka University Medical Center, Beer-Sheva, Israel (broides{at}bgu.ac.il)
 
Next Section

Abstract

Background.This study describes the epidemiologic, microbiologic, and otologic features and selected signs and symptoms of acute otitis media (AOM) caused by Moraxella catarrhalis and compares them with AOM caused by other bacterial pathogens.

Methods.Patients aged <5 years with culture-positive AOM from whom a middle ear fluid specimen was obtained and cultured during 1999–2006 were enrolled in the study.

Results.Of a total of 12,799 AOM episodes, 8198 (64%) were culture positive, with isolation of 10,382 pathogens: Haemophilus influenzae, 4982 (48.0%); Streptococcus pneumoniae, 4450 (42.9%); M. catarrhalis, 501 (4.8%); and group A streptococci, 449 (4.3%). The distribution of single versus mixed M. catarrhalis infection was significantly different compared with the 3 other pathogens (165 cases [32.9%] as a single pathogen of all M. catarrhalis AOM episodes vs 3108 [62.4%] in AOM caused by H. influenzae, 2592 [58.2%] in AOM caused by S. pneumoniae, and 304 [67.7%] in AOM caused by group A streptococci; P<.001for all comparisons). In multivariate analysis, M. catarrhalis AOM was more frequent in patients experiencing their first AOM episode versus recurrent AOM and mixed infections. M. catarrhalis AOM was associated with lower proportions of spontaneous perforation of tympanic membrane compared with all other pathogens. None of the AOM episodes caused by M. catarrhalis was associated with mastoiditis.

Conclusions.Compared with AOM caused by other pathogens, AOM caused by M. catarrhalis is characterized by a higher proportion of mixed infections, younger age at diagnosis, a lower proportion of spontaneous perforation of the tympanic membrane, and no mastoiditis.

The most common pathogens to cause acute otitis media (AOM) in children are Streptococcus pneumoniae, nontypeable Haemophilus influenzae, Moraxella catarrhalis, and group A streptococcus (GAS) [1]. Clinical and otologic aspects of AOM caused by S. pneumoniae, H. influenzae, or GAS have some characteristics that have been previously reported. S. pneumoniae more frequently causes severe AOM with high temperature, more severe otalgia, more frequent tympanic membrane redness and bulging, and higher middle era fluid (MEF) and peripheral blood leukocyte and neutrophil counts [2-7]. H. influenzae AOM is more frequently associated with conjunctivitis, bilateral AOM, previous antibiotic treatment, and recurrent disease [2, 8], and GAS AOM is more often severe in older children and is characterized by higher rates of spontaneous perforation and mastoiditis [9].

M. catarrhalis AOM is usually considered a relatively less virulent pathogen [10], but the clinical features of AOM caused by M. catarrhalis have not been described in detail. Animal models of M. catarrhalis AOM and human studies have suggested a weaker local immune response and fewer structural changes compared with AOM caused by S. pneumoniae or H. influenzae [11-13].

We sought to study the epidemiologic, microbiologic, and selected clinical and otologic features (temperature, vomiting, spontaneous perforation, and presence of mastoiditis at time of diagnosis) of AOM caused by M. catarrhalis . The main objective of the present study was to determine whether these clinical and otologic features of patients with M. catarrhalis AOM are indeedless severe than those of patients with AOM caused by S. pneumoniae, H. influenzae, or GAS.

Previous SectionNext Section

Patients and Methods

Study population and setting. The Negev region is a heterogeneously populated area, with >700,000 inhabitants (of whom >150,000 are children) belonging to 2 major ethnic groups, Jewish and Muslim Bedouin. The Jewish population lifestyle and standards of living can be compared with those of developed countries, whereas overcrowding, lower levels of education, lower income, and larger family size are more common among the Bedouins (a population still in transition from a seminomadic lifestyle to permanent settlement) than among the Jewish population. The Soroka University Medical Center (Beer Sheva, Israel) is the only hospital for the entire region, and its clinical microbiology laboratory provides services to both the hospital and 60% of the community. Thus, 95% of all MEF cultures from patients with AOM in the region are performed in this laboratory [14].

Patients and procedures. We enrolled patients aged <5 years with AOM from whom a specimen of MEF was obtained and cultured during January 1999 to December 2006. Culture specimens were obtained by either tympanocentesis or collection of pus that drained from the ear during the last 7 days before enrollment. The diagnosis of AOM was made by a pediatrician, a family physician, or an otolaryngologist. Demographic and clinical information was prospectively obtained from children with cultures positive for S. pneumoniae, H. influenzae, and/or M. catarrhalis from January 1999 through December 2006 and from children with positive cultures for GAS from November 2001 through December 2006. For each episode, we collected information on the patient's age, sex, and ethnicity; the patient's body temperature; the laterality of the AOM (ie, whether it was unilateral or bilateral); the method of acquisition of the culture specimen (ie, by tympanocentesis or from pus draining from the ear after spontaneous perforation of the middle ear cavity); and the patient's recent history of antibiotic treatment. In addition, data on the presence of vomiting and mastoiditis at diagnosis were recorded. Data were obtained from the medical records, the child's physician, or the child's parents, as appropriate. For an episode of infection to be classified as new, it had to occur ⩾30 days after any previous episode caused by the same organism. If caused by a different organism (including β-lactamase-positive H. influenzae versus β-lactamase-negative H. influenzae or different serotypes of S. pneumoniae ), an episode was classified as new even if it occurred <30 days after the previous episode. None of the patients has been immunized with a pneumococcal conjugate vaccine before enrollment.

Tympanocentesis and transport of specimens. Tympanocentesis was performed by an otolaryngologist as previously described [15].

Bacteriologic analysis. The swabs were plated on trypticase agar containing 5% sheep blood and 5.0 mg/mL of gentamicin and on chocolate agar. The plates were incubated aerobically at 35°C for 48 h. Presumptive identification of the 4 otopathogens has been previously described [15, 16]. Only S. pneumoniae, H. influenzae, M. catarrhalis, and GAS were considered pathogens. An infection was defined as mixed if ⩾2 pathogens were found in cultures of specimens obtained from the same ear or if different pathogens were found in cultures of specimens obtained from different ears during the same visit.

Statistical analysis. Data were recorded using Microsoft Office Access 2000 software (Microsoft). Statistical analysis was performed with SPSS statistical software, version 14.0 (SPSS). Univariate analysis was conducted by comparing variables between M. catarrhalis AOM and AOM caused by other pathogens. Variables included were age, sex, ethnicity, seasonality, previous AOM history, previous antibiotic treatment (during the 48 h preceding enrollment and also during 1 month preceding enrollment), previous tympanocentesis, fever, vomiting, concurrent pneumonia at diagnosis, laterality, and spontaneous perforation. The P value was calculated by the χ2test or Fisher exact test, as appropriate. Relative risk and 95% confidence intervals were used to compare the risk of isolation of M. catarrhalis among age groups. Odds ratios, as estimates of the relative risks from multivariate logistic regression models, were used to define independent risk factors associated with isolation of M. catarrhalis versus other pathogens as single-pathogen infections. Variables found to be significant on univariate analysis (ethnicity, age, previous antibiotic treatment, concurrent pneumonia at diagnosis, and spontaneous perforation) were further submitted to multivariable regression analysis. To determine whether the characteristics of single versus mixed M. catarrhalis AOM remained after adjustment for ethnicity, age, previous antibiotic therapy, concurrent pneumonia at diagnosis, and spontaneous perforation, the Mantel-Haenszel test was used. We calculated 95% exact binomial confidence intervals according to criteria established by Clopper and Pearson [17]. P⩽.05was considered significant for all calculations.

Previous SectionNext Section

Results

A total of 12,799 episodes of AOM were recorded during the 7-year period from January 1999 through December 2006. Of these, culture specimens from 7395 episodes (57.8%) were obtained by tympanocentesis, and culture specimens from 1851 episodes (14.5%) were obtained by collection of pus that drained from the ear; information regarding the source of culture specimen (by tympanocentesis or from spontaneous perforation) was missing for 3553 episodes (27.8%). A total of 7407 episodes (57.9%) occurred in male subjects and 5392 episodes (42.1%) occurred in female subjects (Table 1). Of the 12,793 episodes (99%) for which ethnicity was recorded, 5436 (42.5%) occurred in Jewish children and 7357 (57.5%) occurred in Bedouin children, an ethnic distribution resembling that of the healthy population aged ⩽3 years in southern Israel.

Of the 12,793 episodes, a total of 10,382 pathogens were isolated: H. influenzae, 4982 (48.0%); S. pneumoniae, 4450 (42.9%); M. catarrhalis, 501 (4.8%); and GAS, 449 (4.3%). All M. catarrhalis isolates were β-lactamase producers. Culture-negative AOM was recorded in 4601 episodes (36.0%).

Of the 8198 culture-positive episodes, in 2029 (24.8%) >1 pathogen was involved. Of these, 1553 were mixed infection with S. pneumoniae and H. influenzae, 336 were mixed infection with M. catarrhalis and the other 3 pathogens causing AOM, and 140 were mixed infection with other combinations (without M. catarrhalis ). M. catarrhalis was isolated in 501 (3.9%) of 12,799 episodes, of which 165 (32.9%) of 501 were single-pathogen episodes and 336 (67.1%) were mixed infection episodes. Episodes with combinations of pathogens isolated together with M. catarrhalis included M. catarrhalis and S. pneumoniae (n=113); M. catarrhalis and H. influenzae (n=96); M. catarrhalis and GAS (n=3); M. catarrhalis, S. pneumoniae, and H. influenzae (n=122); M. catarrhalis, S. pneumoniae, and GAS (n=1); and M. catarrhalis, H. influenzae, and GAS (n=1). The distribution of single versus mixed infection for M. catarrhalis was significantly different compared with H . influenzae and S. pneumoniae (165 cases [32.9%] as a single pathogen of all AOM caused by M. catarrhalis vs 3108 [62.4%] in AOM caused by H. influenzae, 2592 [58.2%] in AOM caused by S. pneumoniae, and 304 [67.7%] in AOM caused by GAS; P<.001for all comparisons) (Figure 1). These findings remained significant after adjusting for each of the following variables: age, ethnicity, current antibiotic therapy, first AOM episode, and diagnosis of spontaneous perforation at enrollment (P<.001for all comparisons).

Figure 1
View larger version:
Figure 1

Distribution of single versus mixed infections in acute otitis media episodes caused by Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae, and group A streptococcus (GAS). P<.001between M. catarrhalis and the 3 other pathogens

The mean age (± standard deviation) of all enrolled patients was 12.6±9.7months (11.9±8.9months for culture-positive and 13.7±10.9months for culture-negative patients). The mean ages (± standard deviation) for patients with AOM caused by M. catarrhalis, H. influenzae, S. pneumoniae, and GAS as single pathogens were 9.0±6.7, 11.5±7.9, 11.2±8.7, and 19.3±14.4months, respectively. A higher proportion of single-pathogen M. catarrhalis episodes was recorded in children aged <12 months than in all other single-pathogen episodes (P⩽.001) (Table 1). Previous AOM episodes were reported in significantly lower proportions of single-pathogen M. catarrhalis episodes compared with single-pathogen H. influenzae or S. pneumoniae episodes (74 [45%] of 165, 1864 [60%] of 3108, and 1406 [54%] of 2592, respectively; P⩽.01). Single-pathogen M. catarrhalis episodes were associated with higher proportions of patients previously treated with antibiotics versus single-pathogen GAS episodes (P=.03), lower proportions versus single-pathogen H. influenzae episodes (P<.001), and similar proportions versus single-pathogen S. pneumoniae episodes (P=.10) (Table 1). No significant differences were found in the seasonality of M. catarrhalis AOM as a single pathogen compared with the other 3 pathogens: 111 (67.3%) of 165 during winter season (October-March) versus 2107 (67.8%) of 3108 cases of H. influenzae, 1633 (63.0%) of 2592 cases of S. pneumoniae, and 190 (62.5%) of 304 cases of GAS.

Table 1
View larger version:
Table 1

Epidemiologic and Demographic Data for 8193 Subjects with Culture-Positive Acute Otitis Media

Thirty-one (6%) of the 501 patients with M. catarrhalis AOM were enrolled in 9 double-tympanocentesis studies performed during 1999–2004 evaluating the efficacy of 7 antibiotic drugs. Bacteriologic eradication of the pathogen on days 4–6 of treatment was achieved in 29 patients (94%).

We compared selected clinical data in single and mixed M. catarrhalis episodes to those reported in episodes caused by other pathogens (Table 2). No differences in the proportion of episodes with temperatures ⩾38°C or vomiting were found except for GAS as a single pathogen, for which significantly fewer patients had temperatures ⩾38°C or vomiting (P<.001). Bilateral AOM caused by M. catarrhalis was diagnosed in a significantly higher proportion of episodes compared with GAS (P<.01) but in a comparable proportion of episodes with AOM caused by H. influenzae or S. pneumoniae or their combination. Spontaneous perforation occurred in significantly lower proportions of episodes with M. catarrhalis as a single pathogen compared with each of the other 3 pathogens (P<.001for all comparisons).

Table 2
View larger version:
Table 2

Clinical Data for 8193 Children with Culture-Positive Acute Otitis Media (AOM)

Univariate analysis revealed that Jewish ethnicity, age of <1 year, first AOM episode, and decreased rates of spontaneous perforation were associated with M. catarrhalis AOM. Multivariate analysis revealed that Jewish ethnicity and decreased rates of spontaneous perforation in M. catarrhalis AOM remained significant variables compared with H. influenzae or S. pneumoniae.

Of a total of 23 cases of acute mastoiditis (28 pathogens recovered) recorded during the study period, there were no cases of acute mastoiditis with isolation of M. catarrhalis, compared with 12 of 2592, 6 of 304, and 1 of 3108 associated with S. pneumoniae (as a single pathogen; P=.40), GAS (P=.07), and H. influenzae (P=.80). The 4 additional cases were caused by S. pneumoniae and H. influenzae (n=3) and S . pneumoniae and H. influenzae and GAS (n=1).

Previous SectionNext Section

Discussion

In this comprehensive study of 8198 episodes of culture-positive AOM episodes in children across a 7-year study period, we were able to identify some characteristics of AOM caused by M. catarrhalis. M. catarrhalis AOM was associated with significantly higher proportions of mixed infections and first episodes of AOM and significantly lower rates of spontaneous perforation of the tympanic membrane and no mastoiditis at the time of diagnosis compared with the other 3 AOM pathogens.

Previous studies performed in a rat model of AOM showed that M. catarrhalis caused the mildest histopathologic changes when compared with S. pneumoniae or H. influenzae . These changes included less eustachian tube goblet cell formation and shorter duration of increased density of goblet cells [12], new bone formation, mucosal polyps, or fibrous adhesions [11]. Furthermore, in a study of 61 children with AOM caused by H. influenzae or M. catarrhalis, the local immune response associated with M catarrhalis AOM was milder with less immunogloblin (Ig) G, IgM, and IgA production within MEF when compared with H. influenzae, with less severe purulent response and lower bacterial counts in the MEF [13]. Therefore, it is expected that AOM caused by M. catarrhalis should have milder clinical features compared with S. pneumoniae or H. influenzae AOM. Indeed, we found that AOM caused by M. catarrhalis was associated with significantly lower rates of spontaneous perforation of the tympanic membrane at the time of diagnosis of AOM and did not cause mastoiditis in our patients. Mastoiditis caused by M. catarrhalis as a single pathogen is extremely rare and has been reported only once in the English literature [18]. Furthermore, in a study of 17 children aged <13 years with M. catarrhalis bacteremia, Ahmed et al [19] showed that only 3 of 17 had a temperature >38.5°C and only 7 of 17 had a leukocyte count of >15,000 cells/µL. Coinfection was documented in 6 of 17 patients.

In some reports, an increased proportion of M. catarrhalis isolation from the MEF in AOM has been shown. Kilpi et al [20] have reported an increase from 10% to 23% within 15 years, and a similar pattern has also been reported in the United States [1]. In Costa Rica, the prevalence of M. catarrhalis isolated from the MEF of children with AOM aged 3–144 months increased from 2.5% of all pathogens during 1992–1997 to 7% during 1999–2004 and was most commonly found in children aged <24 months during the dry season [21]. However, in the present study, M. catarrhalis has been consistently found as a single pathogen in only ∼1% of MEF isolates. The reasons for the higher relative importance of M. catarrhalis as a pathogen in AOM in certain geographical areas and the different rates of M catarrhalis AOM in other areas are unknown. However, similar to our findings, a younger age at diagnosis and higher representation of M. catarrhalis in the first episode of AOM have also been reported in Finland [20].

In the present study, M. catarrhalis was associated with mixed infections with ⩾1 of the other 3 AOM pathogens in significantly higher proportions than S. pneumonia, H. influenzae, or GAS. In fact, developing populations (such as American Natives or Australian Aborigines and also the Bedouin population described in our studies) are thought to be more otitis prone and more often have recurrent AOM, chronic suppurative otitis media, or spontaneous perforations of the tympanic membrane [22-24]. This could be related to biofilm production (leading to prolonged colonization and resistance to antibiotics) or other anatomical or genetic mechanisms that might be more common in otitis-prone children [25].

The involvement of M. catarrhalis in mixed infections, its much lower rates of spontaneous perforation, the lack of local complications as mastoiditis, the milder local inflammation process and immune response, and the relatively rare and benign course of M. catarrhalis bacteremia suggests that M. catarrhalis is a less virulent pathogen by itself. This evidence is to be taken into consideration in the present and future era of immunization with the pneumococcal—and, we hope, anti-H. influenzae —vaccines.

Previous SectionNext Section

Acknowledgments

Financial support. Research grants from GlaxoSmithKline and Wyeth (to R.D.).

Potential conflicts of interest. R.D. has received grant or research support from Berna/Crucell, Wyeth, and MSD; has performed scientific consultancy with Berna/Crucell, GlaxoSmithKline, Novartis, Wyeth, Protea, and MSD; has served as a speaker for Berna/Crucell, GlaxoSmithKline, and Wyeth; and is a shareholder in Protea. D.G. has served as a speaker for GSK and Wyeth. E.L. has served as a speaker for GSK. All other authors: no conflicts.

  • Received March 31, 2009.
  • Accepted June 29, 2009.
Previous Section
 

References

  1. ↵
    1. Bluestone C,
    2. Stephenson J,
    3. Martin L
    . Ten-year review of otitis media pathogens. Pediatr Infect Dis J 1992;11:S7-11.
    MedlineWeb of Science
  2. ↵
    1. Palmu AA,
    2. Herva E,
    3. Savolainen H,
    4. Karma P,
    5. Makela PH,
    6. Kilpi TM
    . Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin Infect Dis 2004;38:234-42.
    Abstract/FREE Full Text
    1. Broides A,
    2. Leibovitz E,
    3. Dagan R,
    4. et al
    . Cytology of middle ear fluid during acute otitis media. Pediatr Infect Dis J 2002;21:57-60.
    CrossRefMedlineWeb of Science
    1. Polachek A,
    2. Greenberg D,
    3. Broides A,
    4. Leiberman A,
    5. Dagan R,
    6. Leibovitz E
    . Relationship among peripheral leukocyte counts, etiologic agents and clinical manifestations in acute otitis media. Pediatr Infect Dis J 2004;23:406-13.
    CrossRefMedlineWeb of Science
    1. Leibovitz E,
    2. Satran R,
    3. Dagan R,
    4. et al
    . Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Pediatr Infect Dis J 2003;22:509-14.
    CrossRefMedlineWeb of Science
    1. Rodriguez WJ,
    2. Schwartz RH
    . Streptococcus pneumoniae causes otitis media with higher fever and more redness of tympanic membrane than Haemophilus influenzae or Moraxella catarrhalis. Pediatr Infect Dis J 1999;18:942-4.
    CrossRefMedlineWeb of Science
  7. ↵
    1. McCormick DP,
    2. Lim-Melia E,
    3. Saeed K,
    4. Baldwin CD,
    5. Chonmaitree T
    . Otitis media: can clinical findings predict bacterial or viral etiology? Pediatr Infect Dis J 2000;19:256-8.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Barkai G,
    2. Leibovitz E,
    3. Givon-Lavi N,
    4. Dagan R
    . Potential contribution by nontypable Haemophilus influenzae in protracted and recurrent acute otitis media. Pediatr Infect Dis 2009;28:466-71.
    CrossRefWeb of Science
  9. ↵
    1. Segal N,
    2. Givon-Lavi N,
    3. Leibovitz E,
    4. Yagupsky P,
    5. Leiberman A,
    6. Dagan R
    . Acute otitis media caused by Streptococcus pyogenes in children. Clin Infect Dis 2005;41:35-41.
    Abstract/FREE Full Text
  10. ↵
    1. Coffey JD Jr,
    2. Martin AD,
    3. Booth HN
    . Neisseria catarrhalis in exudate otitis media. Arch Otolaryngol 1967;86:403-406.
    Abstract/FREE Full Text
  11. ↵
    1. Cayé-Thomasen P,
    2. Tos M
    . Histopathologic differences due to bacterial species in acute otitis media. Int J Pediatr Otorhinolaryngol 2002;63:99-110.
    CrossRefMedlineWeb of Science
  12. ↵
    1. Cayé-Thomasen P,
    2. Tos M
    . Eustachian tube gland tissue changes are related to bacterial species in acute otitis media. Int J Pediatr Otorhinolaryngol 2004;68:101-110.
    CrossRefMedlineWeb of Science
  13. ↵
    1. Faden H
    . Comparison of the local immune response to nontypable Haemophilus influenzae (nHI) and Moraxella catarrhalis (MC) during otitis media. Adv Exp Med Biol 1995;371B:733-6.
    Medline
  14. ↵
    1. Dagan R,
    2. Givon-Lavi N,
    3. Shkolnik L,
    4. Yagupsky P,
    5. Fraser D
    . Acute otitis media caused by antibiotic-resistant Streptococcus pneumoniae in southern Israel: implication for immunizing with conjugate vaccines. J Infect Dis 2000;181:1322-9.
    Abstract/FREE Full Text
  15. ↵
    1. Dagan R,
    2. Leibovitz E,
    3. Fliss DM,
    4. et al
    . Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children. Antimicrob Agents Chemother 2000;44:43-50.
    Abstract/FREE Full Text
  16. ↵
    1. Murray PR,
    2. Baron EJ,
    3. Pfaller MA,
    4. Tenover FC,
    5. Yolken RH
    . Manual of clinical microbiolog. 7th ed. Washington, DC: ASM Press; 1995.
  17. ↵
    1. Clopper C,
    2. Pearson E
    . The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934;26:404-13.
    FREE Full Text
  18. ↵
    1. Leskinen K,
    2. Jero J
    . Acute mastoiditis caused by Moraxella catarrhalis. Int J Pediatr Otorhinolaryngol 2003;67:31-3.
    CrossRefMedlineWeb of Science
  19. ↵
    1. Ahmed A,
    2. Broides A,
    3. Givon-Lavi N,
    4. Peled N,
    5. Dagan R,
    6. Greenberg D
    . Clinical and laboratory aspects of Moraxella catarrhalis bacteremia in children. Pediatr Infect Dis J 2008;27:459-61.
    CrossRefMedlineWeb of Science
  20. ↵
    1. Kilpi T,
    2. Herva E,
    3. Kaijalainen T,
    4. Syrjänen R,
    5. Takala AK
    . Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life. Pediatr Infect Dis J 2001;20:654-62.
    CrossRefMedlineWeb of Science
  21. ↵
    1. Guevara S,
    2. Soley C,
    3. Arguedas A,
    4. Porat N,
    5. Dagan R
    . Seasonal distribution of otitis media pathogens among Costa Rican children. Pediatr Infect Dis J 2008;27:12-6.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Butler JC,
    2. Crengles S,
    3. Cheek JE,
    4. et al
    . Emerging infectious diseases among indigenous peoples. Emerg Infect Dis 2001;7:554-5.
    MedlineWeb of Science
    1. Curns AT,
    2. Holman RC,
    3. Shay DK,
    4. et al
    . Outpatient and hospital visits associated with otitis media among American Indian and Alaska native children younger than 5 years. Pediatrics 2002;109:E41-1.
    CrossRefMedline
  24. ↵
    1. Morris PS,
    2. Leach AJ,
    3. Halpin S,
    4. et al
    . An overview of acute otitis media in Australian Aboriginal children living in remote communities. Vaccine 2007;25:2389-93.
    CrossRefMedlineWeb of Science
  25. ↵
    1. Bakaletz LO
    . Bacterial biofilms in otitis media: evidence and relevance. Pediatr Infect Dis J 2007;26:S17-9.
    CrossRefMedlineWeb of Science
| Table of Contents

This Article

  1. Clin Infect Dis. (2009) 49 (11): 1641-1647. doi: 10.1086/647933
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most