5. Microbiology and Immunology

Fritz RS Hayden FG Calfee DP . Nasal cytokine and chemokine responses in experimental influenza A virus infection: Results of a placebo-controlled trial of intravenous zanamivir treatment. J Infect Dis 1999;180:586–93.

Sheeran P Jafri H Carubelli C . Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J 1999;18:115–22.

Bont L Heijnen CJ Kavelaars A . Local interferongamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J Infect Dis 2001;184:355–8.

Hornsleth A Loland L Larsen LB . Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection. J Clin Virol 2001;21:163–70.

Heikkinen T Thint M Chonmaitree T . Prevalence of various respiratory viruses in the middle ear during acute otitis media. N Engl J Med 1999;340:260–4.

El Ahmer OR Raza MW Ogilvie MM Weir DM Blackwell CC . Binding of bacteria to HEp-2 cells infected with influenza A virus. FEMS Immunol Med Microbiol 1999;23:331–41.

Tong HH Fisher LM Kosunick GM DeMaria TF . Effect of adenovirus type 1 and influenza A virus on Streptococcus pneumoniae nasopharyngeal colonization and otitis media in the chinchilla. Ann Otol Rhinol Laryngol 2000;109:1021–7.

Tong HH Chen Y James M Van Deusen J Welling DB DeMaria TF . Expression of cytokine and chemokine genes by human middle ear epithelial cells induced by formalin-killed Haemophilus influenzae or its lipooligosaccharide htrB and rfaD mutants. Infect Immun 2001;69:3678–84.

McCullers JA Bartmess KC . Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 2003;187:1000–9.

Winther B Hayden FG Arruda E Dutkowski R Ward P Hendley JO . Viral respiratory infection in schoolchildren: Effects on middle ear pressure. Pediatrics 2002;109:826–32.

Buchman CA Doyle WJ Pilcher O Gentile DA Skoner DP . Nasal and otologic effects of experimental respiratory syncytial virus infection in adults. Am J Otolaryngol 2002;23:70–5.

Stenfors LE Bye HM Raisanen S . Causes for massive bacterial colonization on mucosal membranes during infectious mononucleosis: Implications for acute otitis media. Int J Pediatr Otorhinolaryngol 2002;65:233–40.

Vesa S Kleemola M Blomqvist S Takala A Kilpi T Hovi T . Epidemiology of documented viral respiratory infections and acute otitis media in a cohort of children followed from two to twenty-four months of age. Pediatr Infect Dis J 2001;20:574–81.

Kotikoski MJ Palmu AA Nokso-Koivisto J Kleemola M . Evaluation of the role of respiratory viruses in acute myringitis in children less than two years of age. Pediatr Infect Dis J 2002;21:636–41.

McCormick DP Lim-Melia E Saeed K Baldwin CD Chonmaitree T . Otitis media: Can clinical findings predict bacterial or viral etiology?. Pediatr Infect Dis J 2000;19:256–8.

Heikkinen T Chonmaitree T . Importance of respiratory viruses in acute otitis media. Clin Microbiol Rev 2003;16:230–41.

Chonmaitree T Henrickson KJ . Detection of respiratory viruses in the middle ear fluids of children with acute otitis media by multiplex reverse transcription: Polymerase chain reaction assay. Pediatr Infect Dis J 2000;19:258–60.

Ishibashi T Monobe H Nomura Y Shinogami M Yano J . Multiplex nested reverse transcription–polymerase chain reaction for respiratory viruses in acute otitis media. Ann Otol Rhinol Laryngol 2003;112:252–7.

Whitley RJ Hayden FG Reisinger KS . Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20:127–33. [Erratum in Pediatr Infect Dis J 2001;20:421.].

Marcotte H Lavoie MC . Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev 1998;62:71–109.

Stenfors LE Raisanen S . Occurrence of middle ear pathogens in the nasopharynx of young individuals. A quantitative study in four age groups. Acta Otolaryngol (Stockh) 1990;109:142–8.

Singh PK Tack BF McCray PB Jr. Welsh MJ . Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 2000;279:L799–L805.

Sobin J Engquist S Nord CE . Bacteriology of the maxillary sinus in healthy volunteers. Scand J Infect Dis 1992;24:633–5.

Stenfors LE . Non-specific and specific immunity to bacterial invasion of the middle ear cavity. Int J Pediatr Otorhinolaryngol 1999;49(suppl 1): S223–S226.

Heikkinen T Chonmaitree T . Increasing importance of viruses in acute otitis media. Ann Med 2000;32:157–63.

Patel J Faden H Sharma S Ogra PL . Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media. Int J Pediatr Otorhinolaryngol 1992;23:15–23.

Bakaletz LO . Viral potentiation of bacterial superinfection of the respiratory tract. Trends Microbiol 1995;3:110–4.

Tano K Grahn-Hakansson E Holm SE Hellstrom S . Inhibition of OM pathogens by alpha-hemolytic streptococci from healthy children, children with SOM and children with rAOM. Int J Pediatr Otorhinolaryngol 2000;56:185–90.

Stenfors LE Raisanen S . The membranous tonsillitis during infectious mononucleosis is nevertheless of bacterial origin. Int J Pediatr Otorhinolaryngol 1993;26:149–55.

Brook I Deleyva F . Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients with infectious mononucleosis. J Med Microbiol 1996;44:131–4.

Lamm ME . Interaction of antigens and antibodies at mucosal surfaces. Annu Rev Microbiol 1997;51:311–40.

Brandtzaeg P . Immunocompetent cells of the upper airway: Functions in normal and diseased mucosa. Eur Arch Otorhinolaryngol 1995;252(suppl 1): S8–S21.

Ivarsson M Lundberg C . Phagocytosis in the nasopharyngeal secretion by cells from the adenoid. Acta Otolaryngol (Stockh) 2001;121:517–22.

Harbitz O Jenssen AO Smidsrod O . Lysozyme and lactoferrin in sputum from patients with chronic obstructive lung disease. Eur J Respir Dis 1984;65:512–20.

Vorland LH . Lactoferrin: A multifunctional glycoprotein. APMIS 1999;107:971–81.

Stenfors LE Raisanen S . Immunoglobulin-coated bacteria on the tonsillar surface during infectious mononucleosis. J Laryngol Otol 1996;110:339–42.

Fluckiger U Jones KF Fischetti VA . Immunoglobulins to group A streptococcal surface molecules decrease adherence to and invasion of human pharyngeal cells. Infect Immun 1998;66:974–9.

Valentin-Weigand P Jungnitz H Zock A Rohde M Chhatwal GS . Characterization of group B streptococcal invasion in HEp-2 epithelial cells. FEMS Microbiol Lett 1997;147:69–74.

Stenfors LE Bye HM Raisanen S Myklebust R . Bacterial penetration into tonsillar surface epithelium during infectious mononucleosis. J Laryngol Otol 2000;114:848–52.

Stroman DW Roland PS Dohar J Burt W . Microbiology of normal external auditory canal. Laryngoscope 2001;111:2054–9.

Senturia BH Gessert CF Carr CD Baumann ES . Studies concerned with tubotympanitis. Ann Otol Rhinol Laryngol 1958;67:440–67.

Liu YS Lang R Lim DJ Birck HG . Microorganisms in chronic otitis media with effusion. Ann Otol Rhinol Laryngol Suppl 1976;85(suppl 25):245–9.

Healy GB Teele DW . The microbiology of chronic middle ear effusions in children. Laryngoscope 1977;87:1472–8.

Riding KH Bluestone CD Michaels RH Cantekin EI Doyle WJ Poziviak CS . Microbiology of recurrent and chronic otitis media with effusion. J Pediatr 1978;93:739–43.

Browning GG . Pathology of inflammatory conditions of the external and middle ear. In: Booth JB , ed. Otology. Vol 3. London, England: Butterworth Heinemann, 1997.

Brook I Frazier EH Thompson DH . Aerobic and anaerobic microbiology of external otitis. Clin Infect Dis 1992;15:955–8.

Sander R . Otitis externa: A practical guide to treatment and prevention. Am Fam Physician 2001;63:927–36, 941–2.

Vartiainen E Vartiainen J . Effect of aerobic bacteriology on the clinical presentation and treatment results of chronic suppurative otitis media. J Laryngol Otol 1996;110:315–8.

Silvola J Palva T . Long-term results of pediatric primary one-stage cholesteatoma surgery. Int J Pediatr Otorhinolaryngol 1999;48:101–7.

Brumfitt W Percival A Williams JD . Estimation of bacteria and cells in urine. Assoc Clin Pathol 1973;8:1–11.

McGinley KJ Leyden JJ Marples RR Kligman AM . Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis. J Invest Dermatol 1975;64:401–5.

Stenfors LE Raisanen S . Quantitative analysis of the bacterial findings in otitis media. J Laryngol Otol 1990;104:749–57.

Raisanen S Stenfors LE . Bacterial quantification — A necessary complement for the comprehension of middle ear inflammations. Int J Pediatr Otorhinolaryngol 1992;23:117–24.

Greiner O Day PJ Bosshard PP Imeri F Altwegg M Nadal D . Quantitative detection of Streptococcus pneumoniae in nasopharyngeal secretions by real-time PCR. J Clin Microbiol 2001;39:3129–34.

Stenfors LE Raisanen S . Quantity of aerobic bacteria in the bony portion of the external auditory canal of children. Int J Pediatr Otorhinolaryngol 2002;66:167–73.

Cabenda SI Peerbooms PG van Asselt GJ Feenstra L van der Baan S . Serous otitis media (SOM). A bacteriological study of the ear canal and the middle ear. Int J Pediatr Otorhinolaryngol 1988;16:119–24.

Costerton JW Watkins L . Adherence of bacteria to foreign bodies: The role of the biofilm. In: Root RK Trunkey DD Sande MA , eds. New surgical and medical approaches in infectious diseases. Vol 6. New York, NY: Churchill Livingstone, 1987:17–30.

Costerton JW Nickel JC Ladd TI . Suitable methods for the comparative study of free-living and surface-associated bacterial populations. In: Poindexter ES Ledbetter ER , eds. Bacteria in nature. New York, NY: Plenum Press, 1986:49.

Sundstrom J Agrup C Kronvall G Wretlind B . Pseudomonas aeruginosa adherence to external auditory canal epithelium. Arch Otolaryngol Head Neck Surg 1997;123:1287–92.

Stone M Fulghum RS . Bactericidal activity of wet cerumen. Ann Otol Rhinol Laryngol 1984;93:183–6.

Boe R Silvola J Yang J . Human beta-defensin-1 mRNA is transcribed in tympanic membrane and adjacent auditory canal epithelium. Infect Immun 1999;67:4843–6.

Jacobs MR . Increasing antibiotic resistance among otitis media pathogens and their susceptibility to oral agents based on pharmacodynamic parameters. Pediatr Infect Dis J 2000;19(suppl): S47–S56.

Dagan R Hoberman A Johnson C . Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media. Pediatr Infect Dis J 2001;20:829–37.

Gehanno P Panajotopoulos A Barry B . Microbiology of otitis media in the Paris, France, area from 1987 to 1997. Pediatr Infect Dis J 2001;20:570–3.

Rodriguez WJ Schwartz RH . Streptococcus pneumoniae causes otitis media with higher fever and more redness of tympanic membranes than Haemophilus influenzae or Moraxella catarrhalis. Pediatr Infect Dis J 1999;18:942–4.

Heikkinen T Ghaffar F Okorodudu AO Chonmaitree T . Serum interleukin-6 in bacterial and nonbacterial acute otitis media. Pediatrics 1998;102:296–9.

Broides A Leibovitz E Dagan R . Cytology of middle ear fluid during acute otitis media. Pediatr Infect Dis J 2002;21:57–61.

Leibovitz E Satran R Piglansky L . Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae?. Pediatr Infect Dis J 2003;22:509–15.

Turner D Leibovitz E Aran A . Acute otitis media in infants younger than two months of age: Microbiology, clinical presentation and therapeutic approach. Pediatr Infect Dis J 2002;21:669–74.

Leiberman A Dagan R Leibovitz E Yagupsky P Fliss DM . The bacteriology of the nasopharynx in childhood. Int J Pediatr Otorhinolaryngol 1999;49(suppl 1): S151–S153.

Long SS Henretig FM Teter MJ McGowan KL . Nasopharyngeal flora and acute otitis media. Infect Immun 1983;41:987–91.

Faden H Duffy L Wasielewski R Wolf J Krystofik D Tung Y . Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics. J Infect Dis 1997;175:1440–5.

Zenni MK Cheatham SH Thompson JM . Streptococcus pneumoniae colonization in the young child: Association with otitis media and resistance to penicillin. J Pediatr 1995;127:533–7.

Mastro TD Ghafoor A Nomani NK . Antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in Pakistan. Lancet 1991;337:156–9.

Lehmann D Gratten M Montgomery J . Susceptibility of pneumococcal carriage isolates to penicillin provides a conservative estimate of susceptibility of invasive pneumococci. Pediatr Infect Dis J 1997;16:297–305.

Lloyd-Evans N O'Dempsey TJ Baldeh I . Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr Infect Dis J 1996;15:866–71.

Hodges RG Macleod CM Bernhard WG . Epidemic pneumococcal pneumonia: III. Pneumococcal carrier studies. Am J Hygiene 1946;44:207–230.

Gray BM Converse GM III Dillon HC Jr. . Epidemiologic studies of Streptococcus pneumoniae in infants: Acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980;142:923–33.

Hendley JO Sande MA Stewart PM Gwaltney JM Jr. . Spread of Streptococcus pneumoniae in families. I. Carriage rates and distribution of types. J Infect Dis 1975;132:55–61.

Montgomery JM Lehmann D Smith T . Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in Highland children of Papua New Guinea. Rev Infect Dis 1990;12(suppl 8): S1006–S1016.

Mastro TD Nomani NK Ishaq Z . Use of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in Pakistan for surveillance for antimicrobial resistance. Pediatr Infect Dis J 1993;12:824–30.

Frederiksen B Henrichsen J . Throat carriage of Streptococcus pneumoniae and Streptococcus pyogenes among infants and children in Zambia. J Trop Pediatr 1988;34:114–7.

Aniansson G Alm B Andersson B . Nasopharyngeal colonization during the first year of life. J Infect Dis 1992;165(suppl 1): S38–S42.

Dunlap MB Harvey HS . Host influence on upper respiratory flora. N Engl J Med 1956;255:640–6.

Loda FA Collier AM Glezen WP Strangert K Clyde WA Jr. Denny FW . Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children. J Pediatr 1975;87:1087–93.

Dagan R Melamed R Muallem M Piglansky L Yagupsky P . Nasopharyngeal colonization in southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: Relation to serotypes likely to be included in pneumococcal conjugate vaccines. J Infect Dis 1996;174:1352–5.

Faden H Waz MJ Bernstein JM Brodsky L Stanievich J Ogra PL . Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. Ann Otol Rhinol Laryngol 1991;100:612–5.

Ingvarsson L Lundgren K Ursing J . The bacterial flora in the nasopharynx in healthy children. Acta Otolaryngol Suppl (Stockh) 1982(suppl 386):94–6.

Howard AJ Dunkin KT Millar GW . Nasopharyngeal carriage and antibiotic resistance of Haemophilus influenzae in healthy children. Epidemiol Infect 1988;100:193–203.

Harabuchi Y Faden H Yamanaka N Duffy L Wolf J Krystofik D . Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics. J Infect Dis 1994;170:862–6.

Faden H Stanievich J Brodsky L Bernstein J Ogra PL . Changes in nasopharyngeal flora during otitis media of childhood. Pediatr Infect Dis J 1990;9:623–6.

Giebink GS . The pathogenesis of pneumococcal otitis media in chinchillas and the efficacy of vaccination in prophylaxis. Rev Infect Dis 1981;3:342–53.

Klugman KP Koornhof HJ Kuhnle V . Clinical and nasopharyngeal isolates of unusual multiply resistant pneumococci. Am J Dis Child 1986;140:1186–90.

Geslin P Buu-Hoi A Fremaux A Acar JF . Antimicrobial resistance in Streptococcus pneumoniae: An epidemiological survey in France, 1970–1990. Clin Infect Dis 1992;15:95–8.

Arason VA Kristinsson KG Sigurdsson JA Stefansdottir G Molstad S Gudmundsson S . Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ 1996;313:387–91.

Leach AJ Shelby-James TM Mayo M . A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis 1997;24:356–62.

Brook I Gober AE . Prophylaxis with amoxicillin or sulfisoxazole for otitis media: Effect on the recovery of penicillin-resistant bacteria from children. Clin Infect Dis 1996;22:143–5.

Abdel-Haq N Abuhammour W Asmar B Thomas R Dabbagh S Gonzalez R . Nasopharyngeal colonization with Streptococcus pneumoniae in children receiving trimethoprim-sulfamethoxazole prophylaxis. Pediatr Infect Dis J 1999;18:647–9.

Dabernat H Geslin P Megraud F . Effects of cefixime or co-amoxiclav treatment on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media. J Antimicrob Chemother 1998;41:253–8.

Cohen R Bingen E Varon E . Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children. Pediatr Infect Dis J 1997;16:555–60.

Cohen R Navel M Granberg J . One dose ceftriaxone vs ten days of amoxicillin/clavulanate therapy for acute otitis media: Clinical efficacy and change in nasopharyngeal flora. Pediatr Infect Dis J 1999;18:403–9.

Dagan R Leibovitz E Greenberg D Yagupsky P Fliss DM Leiberman A . Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients. Pediatr Infect Dis J 1998;17:880–5.

Dagan R Leibovitz E Piglansky L Yagupsky P . Effect of antibiotic treatment on pneumococcal nasopharyngeal carriage during and after acute otitis media: Comparison of three oral drugs. In: Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, Calif: American Society for Microbiology, 1999: abstract 1028.

Melander E Molstad S Persson K Hansson HB Soderstrom M Ekdahl K . Previous antibiotic consumption and other risk factors for carriage of penicillin-resistant Streptococcus pneumoniae in children. Eur J Clin Microbiol Infect Dis 1998;17:834–8.

Dagan R Fraser D Givon N Yagupsky P . Coverage of antibiotic-resistant Streptococcus pneumoniae causing acute otitis media by 7, 9, and 11-valent pneumococcal conjugate vaccines in southern Israel. In: Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, Calif: American Society for Microbiology, 1999: abstract 1038.

Dagan R Leibovitz E Cheletz G Leiberman A Yagupsky P . Antibiotic treatment in acute otitis media induces middle ear fluid super-infection with pre-existing nasopharyngeal antibiotic-resistant Streptococcus pneumoniae. In: Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, Calif: American Society for Microbiology, 1999: abstract 1183.

Principi N Marchisio P Schito GC Mannelli S . Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Ascanius Project Collaborative Group. Pediatr Infect Dis J 1999;18:517–23.

Ghaffar F Friedland IR McCracken GH Jr. . Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J 1999;18:638–46.

Henderson FW Gilligan PH Wait K Goff DA . Nasopharyngeal carriage of antibiotic-resistant pneumococci by children in group day care. J Infect Dis 1988;157:256–63.

Rosen C Christensen P Hovelius B Prellner K . A longitudinal study of the nasopharyngeal carriage of pneumococci as related to pneumococcal vaccination in children attending day-care centres. Acta Otolaryngol (Stockh) 1984;98:524–32.

Givon-Lavi N Dagan R Fraser D Yagupsky P Porat N . Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area. Clin Infect Dis 1999;29:1274–80.

Yagupsky P Porat N Fraser D . Acquisition, carriage, and transmission of pneumococci with decreased antibiotic susceptibility in young children attending a day care facility in southern Israel. J Infect Dis 1998;177:1003–12.

De Lencastre H Kristinsson KG Brito-Avo A . Carriage of respiratory tract pathogens and molecular epidemiology of Streptococcus pneumoniae colonization in healthy children attending day care centers in Lisbon, Portugal. Microb Drug Resist 1999;5:19–29.

Marchisio P Claut L Rognoni A . Differences in nasopharyngeal bacterial flora in children with nonsevere recurrent acute otitis media and chronic otitis media with effusion: Implications for management. Pediatr Infect Dis J 2003;22:262–8.

Brook I Gober AE . In vitro bacterial interference in the nasopharynx of otitis media-prone and non-otitis media-prone children. Arch Otolaryngol Head Neck Surg 2000;126:1011–3.

Hendrixson DR de la Morena ML Stathopoulos C St Geme JW III . Structural determinants of processing and secretion of the Haemophilus influenzae hap protein. Mol Microbiol 1997;26:505–18.

Fink DL Cope LD Hansen EJ Geme JW III . The Hemophilus influenzae Hap autotransporter is a chymotrypsin clan serine protease and undergoes autoproteolysis via an intermolecular mechanism. J Biol Chem 2001;276:39492–500.

Fink DL St Geme JW III . Chromosomal expression of the Haemophilus influenzae Hap autotransporter allows fine-tuned regulation of adhesive potential via inhibition of intermolecular autoproteolysis. J Bacteriol 2003;185:1608–15.

Hendrixson DR St Geme JW III . The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Mol Cell 1998;2:841–50.

Fink DL Green BA St Geme JW III . The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and collagen IV. Infect Immun 2002;70:4902–7.

Fink DL Buscher AZ Green B Fernsten P St Geme JW III . The Haemophilus influenzae Hap autotransporter mediates microcolony formation and adherence to epithelial cells and extracellular matrix via binding regions in the C-terminal end of the passenger domain. Cell Microbiol 2003;5:175–86.

Cutter D Mason KW Howell AP Fink DL Green BA St Geme JW III . Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice. J Infect Dis 2002;186:1115–21.

Krasan GP Cutter D Block SL St Geme JW III . Adhesin expression in matched nasopharyngeal and middle ear isolates of nontypeable Haemophilus influenzae from children with acute otitis media. Infect Immun 1999;67:449–54.

Dawid S Grass S St Geme JW III . Mapping of binding domains of nontypeable Haemophilus influenzae HMW1 and HMW2 adhesins. Infect Immun 2001;69:307–14.

Grass S Buscher AZ Swords WE . The Haemophilus influenzae HMW1 adhesin is glycosylated in a process that requires HMW1C and phosphoglucomutase, an enzyme involved in lipooligosaccharide biosynthesis. Mol Microbiol 2003;48:737–51.

Dawid S Barenkamp SJ St Geme JW III . Variation in expression of the Haemophilus influenzae HMW adhesins: A prokaryotic system reminiscent of eukaryotes. Proc Natl Acad Sci U S A 1999;96:1077–82.

St Geme JW III Cutter D . The Haemophilus influenzae Hia adhesin is an autotransporter protein that remains uncleaved at the C terminus and fully cell associated. J Bacteriol 2000;182:6005–13.

Laarmann S Cutter D Juehne T Barenkamp SJ St Geme JW . The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor. Mol Microbiol 2002;46:731–43.

Harvey HA Swords WE Apicella MA . The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus. J Autoimmun 2001;16:257–62.

Swords WE Buscher BA Ver Steeg Ii K . Nontypeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interaction of lipooligosaccharide with the PAF receptor. Mol Microbiol 2000;37:13–27.

Swords WE Ketterer MR Shao J Campbell CA Weiser JN Apicella MA . Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling. Cell Microbiol 2001;3:525–36.

Swords WE Chance DL Cohn LA Shao J Apicella MA Smith AL . Acylation of the lipooligosaccharide of Haemophilus influenzae and colonization: An htrB mutation diminishes the colonization of human airway epithelial cells. Infect Immun 2002;70:4661–8.

Gorter AD Oostrik J van der Ley P Hiemstra PS Dankert J van Alphen L . Involvement of lipooligosaccharides of Haemophilus influenzae and Neisseria meningitidis in defensin-enhanced bacterial adherence to epithelial cells. Microb Pathog 2003;34:121–30.

Ahren IL Janson H Forsgren A Riesbeck K . Protein D expression promotes the adherence and internalization of nontypeable Haemophilus influenzae into human monocytic cells. Microb Pathog 2001;31:151–8.

Fan X Goldfine H Lysenko E Weiser JN . The transfer of choline from the host to the bacterial cell surface requires glpQ in Haemophilus influenzae. Mol Microbiol 2001;41:1029–36.

Novotny LA Jurcisek JA Pichichero ME Bakaletz LO . Epitope mapping of the outer membrane protein P5-homologous fimbrin adhesin of nontypeable Haemophilus influenzae. Infect Immun 2000;68:2119–28.

Hill DJ Toleman MA Evans DJ Villullas S Van Alphen L Virji M . The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1. Mol Microbiol 2001;39:850–62.

Ahren IL Williams DL Rice PJ Forsgren A Riesbeck K . The importance of a beta-glucan receptor in the nonopsonic entry of nontypeable Haemophilus influenzae into human monocytic and epithelial cells. J Infect Dis 2001;184:150–8.

Lim DJ Chun YM Lee HY . Cell biology of tubotympanum in relation to pathogenesis of otitis media — A review. Vaccine 2000;19(suppl 1): S17–S25.

Moon SK Lee HY Li JD . Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1 alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells. Biochim Biophys Acta 2002;1590:41–51.

Lysenko ES Gould J Bals R Wilson JM Weiser JN . Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 2000;68:1664–71.

Starner TD Swords WE Apicella MA McCray PB Jr. . Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation. Infect Immun 2002;70:5287–9.

Craig JE Cliffe A Garnett K High NJ . Survival of nontypeable Haemophilus influenzae in macrophages. FEMS Microbiol Lett 2001;203:55–61.

Craig JE Nobbs A High NJ . The extracytoplasmic sigma factor, final sigma(E), is required for intracellular survival of nontypeable Haemophilus influenzae in J774 macrophages. Infect Immun 2002;70:708–15.

Jedrzejas MJ . Pneumococcal virulence factors: Structure and function. Microbiol Mol Biol Rev 2001;65:187–207.

Tettelin H Nelson KE Paulsen IT . Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 2001;293:498–506.

Musser JM Kaplan SL . Pneumococcal research transformed. N Engl J Med 2001;345:1206–7.

Tong HH Weiser JN James MA DeMaria TF . Effect of influenza A virus infection on nasopharyngeal colonization and otitis media induced by transparent or opaque phenotype variants of Streptococcus pneumoniae in the chinchilla model. Infect Immun 2001;69:602–6.

Cundell DR Weiser JN Shen J Young A Tuomanen EI . Relationship between colonial morphology and adherence of Streptococcus pneumoniae. Infect Immun 1995;63:757–61.

Rosenow C Ryan P Weiser JN . Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 1997;25:819–29.

Holmes AR McNab R Millsap KW . The pavA gene of Streptococcus pneumoniae encodes a fibronectin-binding protein that is essential for virulence. Mol Microbiol 2001;41:1395–408.

Balachandran P Brooks-Walter A Virolainen-Julkunen A Hollingshead SK Briles DE . Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae. Infect Immun 2002;70:2526–34.

Magee AD Yother J . Requirement for capsule in colonization by Streptococcus pneumoniae. Infect Immun 2001;69:3755–61.

Berry AM Paton JC . Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect Immun 2000;68:133–40.

Tong HH Blue LE James MA DeMaria TF . Evaluation of the virulence of a Streptococcus pneumoniae neuraminidase-deficient mutant in nasopharyngeal colonization and development of otitis media in the chinchilla model. Infect Immun 2000;68:921–4.

Murdoch C Read RC Zhang Q Finn A . Choline-binding protein A of Streptococcus pneumoniae elicits chemokine production and expression of intercellular adhesion molecule 1 (CD54) by human alveolar epithelial cells. J Infect Dis 2002;186:1253–60.

Hammerschmidt S Bethe G Remane PH Chhatwal GS . Identification of pneumococcal surface protein A as a lactoferrin-binding protein of Streptococcus pneumoniae. Infect Immun 1999;67:1683–7.

Hammerschmidt S Tillig MP Wolff S Vaerman JP Chhatwal GS . Species-specific binding of human secretory component to SpsA protein of Streptococcus pneumoniae via a hexapeptide motif. Mol Microbiol 2000;36:726–36.

Overweg K Pericone CD Verhoef GG . Differential protein expression in phenotypic variants of Streptococcus pneumoniae. Infect Immun 2000;68:4604–10.

Spellerberg B Cundell DR Sandros J . Pyruvate oxidase, as a determinant of virulence in Streptococcus pneumoniae. Mol Microbiol 1996;19:803–13.

Throup JP Koretke KK Bryant AP . A genomic analysis of two-component signal transduction in Streptococcus pneumoniae. Mol Microbiol 2000;35:566–76.

Lau GW Haataja S Lonetto M . A functional genomic analysis of type 3 Streptococcus pneumoniae virulence. Mol Microbiol 2001;40:555–71.

Wizemann TM Heinrichs JH Adamou JE . Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect Immun 2001;69:1593–8.

Marra A Asundi J Bartilson M . Differential fluorescence induction analysis of Streptococcus pneumoniae identifies genes involved in pathogenesis. Infect Immun 2002;70:1422–33.

Passalacqua G Canonica GW . Treating the allergic patient: Think globally, treat globally. Allergy 2002;57:876–83.

Johansson SG Hourihane JO Bousquet J . A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001;56:813–24. [Erratum in Allergy 2001;56:1229.].

Phillips MJ Knight NJ Manning H Abbott AL Tripp WG . IgE and secretory otitis media. Lancet 1974;2:1176–8.

Wright ED Hurst D Miotto D Giguere C Hamid Q . Increased expression of major basic protein (MBP) and interleukin-5(IL-5) in middle ear biopsy specimens from atopic patients with persistent otitis media with effusion. Otolaryngol Head Neck Surg 2000;123:533–8.

Jang CH Kim YH . Demonstration of RANTES and eosinophilic cataionic protein in otitis media with effusion with allergy. Int J Pediatr Otorhinolaryngol 2003;67:531–3.

Hurst DS Venge P . Evidence of eosinophil, neutrophil, and mast-cell mediators in the effusion of OME patients with and without atopy. Allergy 2000;55:435–41.

Amin K Hurst DS Roomans GM Venge P Seveus L . Eosinophils and neutrophils in biopsies from the middle ear of atopic children with otitis media with effusion. Inflamm Res 1999;48:626–31.

Hurst DS Weekley M Ramanarayanan MP . Evidence of possible localized specific immunoglobulin E production in middle ear fluid as demonstrated by ELISA testing. Otolaryngol Head Neck Surg 1999;121:224–30.

Jang CH Kim YH . Characterization of cytokines present in pediatric otitis media with effusion: Comparison of allergy positive and negative. Int J Pediatr Otorhinolaryngol 2002;66:37–40.

Irander K Borres MP Bjorksten B . Middle ear diseases in relation to atopy and nasal metachromatic cells in infancy. Int J Pediatr Otorhinolaryngol 1993;26:1–9.

Alho OP Koivu M Sorri M Rantakallio P . Risk factors for recurrent acute otitis media and respiratory infection in infancy. Int J Pediatr Otorhinolaryngol 1990;19:151–61.

Labadie RF Jewett BS Hart CF Prazma J Pillsbury HC III . Allergy increases susceptibility to otitis media with effusion in a rat model. Otolaryngol Head Neck Surg 1999;121:687–92.

Denburg JA . Microenvironmental influences on inflammatory cell differentiation. Allergy 1995;50(suppl):25–8.

Takeuchi K Fujita Y Tomemori T Yuta A Iriyoshi N Sakakura Y . Analysis of T cell receptor beta chain repertoire in middle ear effusions. Ann Otol Rhinol Laryngol 1996;105:213–7.

Bikhazi P Ryan AF . Expression of immunoregulatory cytokines during acute and chronic middle ear immune response. Laryngoscope 1995;105:629–34.

Hurst DS Venge P . Levels of eosinophil cationic protein and myeloperoxidase from chronic middle ear effusion in patients with allergy and/or acute infection. Otolaryngol Head Neck Surg 1996;114:531–44.

Ohashi Y Nakai Y Tanaka A Kakinoki Y Washio Y . Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion. Clin Otolaryngol 1998;23:231–4.

Takeuchi K Maesako K Yuta A Sakakura Y . Interleukin-8 gene expression in middle ear effusions. Ann Otol Rhinol Laryngol 1994;103:404–7.

Maxwell KS Fitzgerald JE Burleson JA Leonard G Carpenter R Kreutzer DL . Interleukin-8 expression in otitis media. Laryngoscope 1994;104:989–95.

Friedman RA Doyle WJ Casselbrant ML Bluestone C Fireman P . Immunologic-mediated eustachian tube obstruction: A double-blind crossover study. J Allergy Clin Immunol 1983;71:442–7.

Skoner DP Doyle WJ Fireman P . Eustachian tube obstruction (ETO) after histamine nasal provocation — A double-blind dose-response study. J Allergy Clin Immunol 1987;79:27–31.

Demoly P Crampette L Mondain M . Assessment of inflammation in noninfectious chronic maxillary sinusitis. J Allergy Clin Immunol 1994;94:95–108.

Stenstrom C Ingvarsson L . General illness and need of medical care in otitis prone children. Int J Pediatr Otorhinolaryngol 1994;29:23–32.

Naclerio RM Meier HL Kagey-Sobotka A . Mediator release after nasal airway challenge with allergen. Am Rev Respir Dis 1983;128:597–602.

Gosset P Tillie-Leblond I Malaquin F Durieu J Wallaert B Tonnel AB . Interleukin-8 secretion in patients with allergic rhinitis after an allergen challenge: Interleukin-8 is not the main chemotactic factor present in nasal lavages. Clin Exp Allergy 1997;27:379–88.

Lampinen M Rak S Venge P . The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 1999;29:314–22.

Sehmi R Cromwell O Wardlaw AJ Moqbel R Kay AB . Interleukin-8 is a chemo-attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects. Clin Exp Allergy 1993;23:1027–36.

Tomonaga K Kurono Y Mogi G . The role of nasal allergy in otitis media with effusion. A clinical study. Acta Otolaryngol Suppl (Stockh) 1988(suppl 458):41–7.

Jero J Virolainen A Virtanen M Eskola J Karma PH . Factors predicting poor outcome of acute otitis media in children. In: Lim DJ Bluestone CD Casselbrant M Klein JO Ogra PL , eds. Proceedings of the Sixth International Symposium on Recent Advances in Otitis Media. Hamilton, Canada: BC Decker, 1996:78–80.

Becker S Koch T Philipp A . Allergic origin of recurrent middle ear effusion and adenoids in young children [in German]. HNO 1991;39:182–4.

Nsouli TM Nsouli SM Linde RE O'Mara F Scanlon RT Bellanti JA . Role of food allergy in serous otitis media. Ann Allergy 1994;73:215–9.

Hurst DS . Association of otitis media with effusion and allergy as demonstrated by intradermal skin testing and eosinophil cationic protein levels in both middle ear effusions and mucosal biopsies. Laryngoscope 1996;106:1128–37.

Hall LJ Lukat RM . Results of allergy treatment on the eustachian tube in chronic serous otitis media. Am J Otol 1981;3:116–21.

McMahan JT Calenoff E Croft DJ Barenholtz L Weber LD . Chronic otitis media with effusion and allergy: Modified RAST analysis of 119 cases. Otolaryngol Head Neck Surg 1981;89:427–31.

Draper WL . Secretory otitis media in children: A study of 540 children. Laryngoscope 1967;77:636–53.

Fernandez AA McGovern JP . Secretory otitis media in allergic infants and children. South Med J 1965;58:581–6.

Hurst DS . Allergy management of refractory serous otitis media. Otolaryngol Head Neck Surg 1990;102:664–9.

Psifidis A Hatzistilianou M Samaras K Aggouridaki C Daniilidis J Catriu D . Atopy and otitis media in children. In: Ruben RJ Karma PH , eds. Proceedings of the Seventh International Congress of Pediatric Otorhinolaryngology. Amsterdam, the Netherlands: Elsevier Science, 1998:205.

Shubich I . Otitis media with effusion and allergy control in children: A prospective study. In: Lim DJ Bluestone CD , eds. Proceedings of the Sixth International Symposium on Recent Advances in Otitis Media. Hamilton, Canada: BC Decker, 1995:173–4.

Hurst DS Amin K Seveus L Venge P . Evidence of mast cell activity in the middle ears of children with otitis media with effusion. Laryngoscope 1999;109:471–7.

Hou Y Hu WG Hirano T Gu XX . A new intra-NALT route elicits mucosal and systemic immunity against Moraxella catarrhalis in a mouse challenge model. Vaccine 2002;20:2375–81.

Velge-Roussel F Marcelo P Lepage AC Buzoni-Gatel D Bout DT . Intranasal immunization with Toxoplasma gondii SAG1 induces protective cells into both NALT and GALT compartments. Infect Immun 2000;68:969–72.

Sabirov A Kodama S Hirano T Suzuki M Mogi G . Intranasal immunization enhances clearance of nontypeable Haemophilus influenzae and reduces stimulation of tumor necrosis factor alpha production in the murine model of otitis media. Infect Immun 2001;69:2964–71.

Suenaga S Kodama S Ueyama S Suzuki M Mogi G . Mucosal immunity of the middle ear: Analysis at the single cell level. Laryngoscope 2001;111:290–6.

Kodama S Suenaga S Hirano T Suzuki M Mogi G . Induction of specific immunoglobulin A and Th2 immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization. Infect Immun 2000;68:2294–300.

Kawauchi H Yamada T Ishimitsu R Ogasawara K . The immunological interaction between activated nasopharyngeal mucosal immune system and adjacent tubotympanal or tracheal mucosal linings upon antigenic exposure. In: Lim DJ Bluestone CD Casselbrant ML , eds. Abstracts of the Eighth International Symposium on Recent Advances in Otitis Media, Ft Lauderdale, Fla, 2003:207.

Golenbock D . Macrophage activation in the middle ear during acute otitis media: Is there a fly in there? In: Lim DJ Bluestone CD Casselbrant ML , eds. Abstracts of the Eighth International Symposium on Recent Advances in Otitis Media, Ft Lauderdale, Fla, 2003:35.

Kawauchi H Ishimitsu R Murata A Takahashi A . Roles of toll-like receptors in IL-15 production by upper respiratory epithelial cells. In: Lim DJ Bluestone CD Casselbrant ML , eds. Abstracts of the Eighth International Symposium on Recent Advances in Otitis Media, Ft Lauderdale, Fla, 2003:318.

Kawauchi H Takahashi A Ishimitsu R Murata A . Antihistamine inhibits IL-8 production from upper respiratory tract epithelial cells. In: Lim DJ Bluestone CD Casselbrant ML , eds. Abstracts of the Eighth International Symposium on Recent Advances in Otitis Media, Ft Lauderdale, Fla, 2003:273.

Kerakawauchi H Kurono Y Mogi G . Immune responses against Streptococcus pyogenes in human palatine tonsils. Laryngoscope 1997;107:634–9.

Kawauchi H Sano K Shiba H . T-cell mucosal immunity in the nasopharynx. In: Veldman JE Passàli D Lim DJ , eds. New frontiers in immunobiology. The Hague, the Netherlands: Kugler Publications, 2000:35–41.