Abstract

The broad, long term of this proposal is to gain an understanding of the mechanism(s) of recurrent otitis media with effusion (OME) due to nontypable Haemophilus influenzae (NTHI). The four specific aims of the project are: 1) Characterize the pattern of nasopharyngeal (NP) carriage of NTHI from birth to one year of age in otitis prone (OP) and nonotitis prone (NOP) children. 2) Identify the host factors that are associated with NP carriage of NTHI. 3) Critically examine the immune response to NTHI among individuals with two or more documented episodes of OME due to different strains of NTHI. 4) Determine the IgG subclasses of antibody that are responsible for the bactericidal activity to NTHI. The first two specific aims will be addressed in a prospective longitudinal study of children who will be followed from birth through the age of two years. The NP carriage of NTHI will be monitored and related tot he incidence of OME. NTHI strains will be characterized by the pattern of outer membrane proteins (OMP) to distinguish newly acquired strains from older strains. Environmental and host factors that affect carriage will be assessed. For example, the ability of respiratory tract epithelium to permit NTHI adherence will be determined by in vitro studies with buccal epithelial cells from OP and NOP children. Differences in the local immune response to NTHI will be characterized by measuring the NTHI specific IgG, M, A and secretory A in NP secretions with an immunodot assay. The second two specific aims will be addressed by studying clinical specimens obtained during the original grant. Acute and convalescent sera from children will be examined for strain specific as well as cross reacting bactericidal antibody. The presence of and bactericidal activity of IGG antibody to specific OMPs, in particular P6/PAL, will be evaluated by Western blot and immunodot analysis. The IgG subclasses of antiNTHI antibody responsible for bactericidal antibody will be determined in meddle ear fluid and serum by ELISA methodology. A better understanding of the immune response to NTHI will hasten the development of an effective vaccine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019679-09
Application #
2197852
Study Section
Hearing Research Study Section (HAR)
Project Start
1986-01-01
Project End
1995-12-31
Budget Start
1994-01-01
Budget End
1995-12-31
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
State University of New York at Buffalo
Department
Pediatrics
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260

  Publications

Faden, H; Duffy, L; Foels, T et al. (1996) Adherence of nontypeable Haemophilus influenzae to respiratory epithelium of otitis-prone and normal children. Ann Otol Rhinol Laryngol 105:367-70
Kodama, H; Faden, H; Harabuchi, Y et al. (1996) Adenoid lymphocyte responses to outer membrane protein P6 of nontypable Haemophilus influenzae in children with and without otitis media. Acta Otolaryngol Suppl 523:153-4
Faden, H; Duffy, L; Williams, A et al. (1995) Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life. J Infect Dis 172:132-5
Faden, H; Harabuchi, Y; Hong, J J (1994) Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media. J Infect Dis 169:1312-7
Harabuchi, Y; Faden, H; Yamanaka, N et al. (1994) Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics. J Infect Dis 170:862-6
Bernstein, J M; Faden, H F; Dryja, D M et al. (1993) Micro-ecology of the nasopharyngeal bacterial flora in otitis-prone and non-otitis-prone children. Acta Otolaryngol 113:88-92
Faden, H; Bernstein, J; Brodsky, L et al. (1992) Effect of prior antibiotic treatment on middle ear disease in children. Ann Otol Rhinol Laryngol 101:87-91
Bernstein, J M; Faden, H S; Loos, B G et al. (1992) Recurrent otitis media with non-typable Haemophilus influenzae: the role of serum bactericidal antibody. Int J Pediatr Otorhinolaryngol 23:1-13
Duffy, L C; Zielezny, M A; Marshall, J R et al. (1991) Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease. Behav Med 17:101-10
Faden, H; Waz, M J; Bernstein, J M et al. (1991) Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. Ann Otol Rhinol Laryngol 100:612-5

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