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Biomedical subjects

H Faden

Publications and source records attributed to H Faden.

At least 19 recordsLinked to original sources

The microbiologic and immunologic basis for recurrent otitis media in children.

UNLABELLED: Otitis media is very common in children. A subpopulation of children, representing 5-10% of the general population, are otitis prone and they experience 4 or more episodes of acute otitis media (AOM) in the first year of life. Nasopharyngeal colonization with the three major middle ear pathogens, S. pneumoniae, nontypeable H. influenzae and M. catarrhalis is frequent in otitis prone children and is directly related to the frequency of AOM. Colonization stimulates the production of mucosal as well as serum antibodies to the pathogens. Specific IgA mucosal antibody limits the duration and frequency of colonization. Serum IgG antibody protects children against the development of otitis media but does not affect colonization. Antibody detected in the middle ear often reflects passive transfer from serum rather than local production. Antibody responses to the three pathogens following AOM are generally reduced in the first 2 years of life and rise rapidly thereafter. There are many different strains of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Among the different strains, there are heterologous surface antigens and some conserved antigens. Conserved antigens induce broadly protective antibodies while strain specific antigens induce limited protection. Although otitis prone children may display strain specific immunity, they often fail to develop a broadly protective antibody response. This subtle immunologic defect makes them susceptible to recurrent and persistent otitis media. CONCLUSIONS: Otitis media is common. Otitis prone children appear to display a subtle immunologic abnormality that predisposes them to recurrent infections. Recent advances in vaccine development may reduce the frequency of otitis media in the general population but the impact on otitis prone children remains unknown.

Acute Disease↗

A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides.

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies. The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples. Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F. The overall mean percent coefficients of variation in this interlaboratory study for all five selotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 3/% for IgM, and 36% for IgA. This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines.

Enzyme-Linked Immunosorbent Assay↗

Urinary findings in asymptomatic subjects with spina bifida treated with intermittent catheterization.

The urines from 43 asymptomatic children with spina bifida were examined. Eighty-one percent were abnormal because of bacteriuria and pyuria (51%), bacteriuria alone (26%) or pyuria alone (5%). Interleukin-8 was elevated in 54% of the abnormal urines. The presence of pyuria and interleukin 8 suggests that the asymptomatic bacteriuria reflects low grade infection rather than colonization.

Adolescent↗

Vaccination strategies for mucosal immune responses.

Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans.

Bacteria↗

Outcome of acute otitis media and its relation to clinical features and nasopharyngeal colonization at the time of diagnosis.

Children (n = 115; age range 1-9 years) with a diagnosis of acute otitis media (AOM) were eligible for this study and were enrolled within 24 h of the onset of symptoms/signs. A nasopharyngeal culture was obtained at the initial visit. Children were treated with a single oral antibiotic for 7 days. Changes in symptoms/signs and tympanic membrane features assessed by a scoring system were monitored for 1 month and related to the nasopharyngeal pathogen recovered on Day 1. More than 80% of children had no symptoms/signs by Day 3, and 60% of cases had normal tympanic membranes by Day 29. Children without any symptoms/signs on Day 3 had significantly lower symptom/sign scores on Day 1 (p = 0.005). Seventy-nine percent of cases carried middle ear pathogens in the nasopharynx at diagnosis: Streptococcus pneumoniae (48%); Haemophilus influenzae (24%); and Moraxella catarrhalis (16%). Children with S. pneumoniae showed significantly higher tympanic membrane scores than children with no pathogen at Days 8, 15 and 29 (p < 0.01 for each comparison). Multivariate regression analysis revealed that lower tympanic membrane score on Day 1, the absence of S. pneumoniae in the nasopharynx and treatment with amoxillin were independent factors for rapid normalization of the tympanic membrane. These data suggest that the clinical course of AOM may be predicted, in part, at the time of diagnosis by means of careful evaluation of symptoms/signs and the tympanic membrane as well as knowledge of pathogens harbored in the nasopharynx.

Acoustic Impedance Tests↗

Immune response to surface protein A of Streptococcus pneumoniae and to high-molecular-weight outer membrane protein A of Moraxella catarrhalis in children with acute otitis media.

The immune response was evaluated in 11 children with Streptococcus pneumoniae and in 9 children with Moraxella catarrhalis otitis media. The age of the children had a range of 4-32 months. The mean IgG, IgM, and IgA antibody responses to surface protein A (PspA) of S. pneumoniae in sera from children at the acute and convalescent stages were 4864 versus 5831 ng/mL, P<.05, 1075 versus 3752 ng/mL, P<.05, and 67 versus 93 ng/mL, nonsignificant (NS), respectively. The mean IgG, IgM, and IgA antibody responses to the high-molecular-weight outer membrane protein (UspA) of M. catarrhalis in sera from children at acute and convalescent stages were 710 versus 935 mg/mL, NS; 1895 versus 2646 ng/mL, NS; and 121 versus 204 ng/mL, P<.05, respectively. These data show that PspA and UspA are immunogenic in children after otitis media.

Acute Disease↗

Immune responses to specific antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the respiratory tract.

Streptococcus pneumoniae and Moraxella catarrhalis are two common respiratory pathogens, colonizing as many as 54 and 72% of children, respectively, by 1 year of age. The immune responses to surface protein A of S. pneumoniae (PspA) and the high-molecular-weight outer membrane protein of M. catarrhalis (UspA) in the sera of various age groups in the general population and in the nasopharynges of 30 children monitored from birth through 1 year of age were evaluated. Immunoglobulin G (IgG) was the dominant serum antibody to PspA and UspA. Whereas the serum antibody response to PspA peaked in childhood, the antibody response to UspA peaked in adulthood. In the first 2 years of life, comparable amounts of IgM and IgG antibodies to both proteins were observed. In older persons, IgG antibodies to both antigens predominated over IgM antibodies. The levels of IgA antibody to these antigens in serum remained low during the first 2 years of life. The levels of IgM antibody to the two antigens in serum exceeded the levels of IgA antibody to the same two antigens throughout life. Although IgA was the dominant antibody to PspA and UspA in airway secretions, it was detected in a minority of the children (3 of 15 for PspA and 0 of 15 for UspA). Even the majority of the children previously colonized with these pathogens lacked antibody to them in their secretions.

Adult↗

Antibody responses to the outer membrane protein P6 of non-typeable Haemophilus influenzae and pneumococcal capsular polysaccharides in otitis-prone children.

Acute otitis media (AOM) is a common infectious disease in children. Some children experience recurrent episodes of AOM. Recent investigations demonstrate antigen-specific immunological deficiencies in children prone to AOM. In the present study, the immune responses to non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (S. pneumoniae) were further investigated in otitis-prone children and normal children. Forty-eight percent of otitis-prone children exhibited reduced IgG2 levels to S. pneumoniae and 55% exhibited reduced IgG levels to NTHi. These data suggest that otitis proneness appears to be related to numerous immunological derangements. Pathogen-specific antibodies are a reliable measure of otitis proneness.

Acute Disease↗

Cellular immune response of adenoidal and tonsillar lymphocytes to the P6 outer membrane protein of non-typeable Haemophilus influenzae and its relation to otitis media.

Cellular immune responses to the P6 outer membrane protein of non-typeable Haemophilus influenzae (NTHi) were determined in vitro by measuring immunoglobulin (Ig) secreting cells and lymphocyte proliferation in adenoidal and tonsillar lymphocytes from 19 children. Preliminary tests showed that P6 did not stimulate naive cells such as cord blood lymphocytes, but did stimulate sensitized cells in adenoids and tonsils. Cellular proliferation was significantly higher in adenoidal lymphocytes than in tonsillar lymphocytes (median: quadratile of stimulation index = 3.7:2.3-5.5 vs. 1.2:1.0-2.1, p < 0.02). A comparison between children with or without otitis media revealed that proliferative responses to P6 of adenoidal lymphocytes from children with otitis media were significantly decreased (2.0:1.8-3.6 vs. 3.7:2.3-5.5, p < 0.04). P6-specific antibody secreting cells were identified in a total of 14 adenoids and the number of cells secreting IgA was decreased in the otitis media group compared to controls (median: quadratile/10(6) cells = 435:359-499 vs. 755:593-1870, p < 0.05). Cultivation with P6 stimulated IgA secretion in children without otitis media, while no response was seen in children with otitis media (median: quadratile/10(6) cells = 1323:915-2410 vs. 2240:1900-2830, p < 0.02). These preliminary data demonstrate that lymphocytes from adenoids and tonsils recognize P6 as a specific antigen and that the adenoid is the more reactive of the two organs. Impaired P6-specific cellular immune responses of adenoids in children with otitis media may explain the recurrent nature of otitis media due to NTHi in the otitis prone population.

Acute Disease↗

Serum antibodies specific to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in children with otitis media with effusion.

We measured the levels of serum IgG antibodies to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in 168 children with otitis media with effusion (OME) who were followed prospectively, using ELISA. Serum IgG antibodies to CD, P6 and pneumococcal capsular polysaccharides were detected in all samples. The anti-pneumococcal polysaccharides antibody level was highest, followed by the anti-P6 antibody level and anti-CD antibody was lowest (median:interquartile ranges were 45.9:19.1-100 microg/ml, 15.6:9.70-23.2 microg/ml and 1.06:0.73-1.87 microg/ml, respectively). In children aged 0-6 years, there were positive correlations among the antibody levels (anti-CD vs anti-P6, r=0.325, p <0.001; anti-CD vs anti-polysaccharide, r=0.397, p <0.0001; anti-P6 vs anti-polysaccharide, r=0.175, p=0.057). However, no relationship was seen in children aged 7-15 years. Children were classified according to severity of OME during the 1-year follow-up. In children aged 0-6 years, the severity of OME correlated inversely with the levels of anti-CD antibody (r=-.23, p=0.012), of anti-P6 antibody (r=-0.292, p=0.0015), and of anti-pneumococcal polysaccharides antibody (r=-0.25, p=0.0064). However, no correlation was found between antibody levels and severity of OME in children aged 7-15 years. These data suggest that persistence and/or recurrence of OME may be due to an insufficient serum antibody response to middle ear pathogens in young children.

Adolescent↗

Molecular characterization of pneumococcal nasopharynx isolates collected from children during their first 2 years of life.

Pneumococcal colonization was studied in 19 children monitored from birth through the age of 2 years. For this purpose, pneumococcal isolates were characterized by capsular typing, restriction fragment end labeling (RFEL), and penicillin-binding protein (PBP) genotyping. Fifty-eight isolates were collected and were found to belong to 10 capsular types, 31 RFEL types, and 7 PBP genotypes. Thirty-nine percent of the isolates had reduced susceptibility to penicillin. All seven highly resistant strains (MICs, > 1 microgram/ml) were identical to the pandemic clone 23F. Children were culture positive between one and eight times at 13 scheduled visits. Although the infants were frequently recolonized with different strains, colonization with one particular strain often persisted for several months. Isolation of a previously detected capsular type was common, and the chromosomal homogeneity tended to be high when it occurred. Horizontal transfer of capsular genes between strains of different RFEL types was demonstrated in one child. The ecological advantage of transfer of capsular genes is unclear unless survival of the organism on a mucosal surface may be linked to immunoprotective pressure against particular capsular types.

Anti-Bacterial Agents↗

Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics.

Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the predominant bacteria associated with otitis media. A cohort of 306 infants was followed from birth through 12 months to determine frequency and duration of colonization and risk of acute otitis media (AOM) and otitis media with effusion (OME). M. catarrhalis was the most common bacterium isolated. Infants colonized at < or = 3 months of age were at increased risk of AOM and OME. Early colonization with M. catarrhalis revealed the greatest risk (relative risk [RR] = 1.24), especially for OME (RR = 1.57). There was a strong relationship between the frequency of colonization and OM (r = .37, P < .001,) for each pathogen. Although S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis are part of the normal nasopharyngeal flora during infancy, an increased rate of colonization may identify a subpopulation of children that is at increased risk of OM.

Acute Disease↗

Exclusive breastfeeding protects against bacterial colonization and day care exposure to otitis media.

OBJECTIVE: We followed a cohort (N = 306) of infants at well-baby visits in two suburban pediatric practices to assess the relation of exclusive breastfeeding, and other environmental exposures, to episodes of acute otitis media (AOM) and otitis media with effusion (OME). METHODS: Detailed prospective information about the exclusiveness of breastfeeding, parental smoking, day care attendance, and family history was obtained at scheduled clinic visits. Tympanometric and otoscopic examinations were used in the diagnosis of otitis media (OM). Nasopharyngeal cultures were performed at 1-6 months, and at 8, 10, 12, 15, 18, and 24 months of age to detect colonization with middle-ear pathogens. RESULTS: Between 6 and 12 months of age, cumulative incidence of first OM episodes increased from 25% to 51% in infants exclusively breastfed and from 54% to 76% in infants formula-fed from birth. Peak incidence of AOM and OME episodes was inversely related to rates of breastfeeding beyond 3 months of age. A twofold elevated risk of first episodes of AOM or OME was observed in exclusively formula-fed infants compared with infants exclusively breast-fed for 6 months. In the logistic regression analysis, formula-feeding was the most significant predictor of AOM and OME episodes, although age at colonization with middle-ear pathogens and day care (outside the home) were significant competing risk factors. A hazard health model suggested additionally that breastfeeding, even for short durations (3 months), reduced onset of OM episodes in infancy. CONCLUSIONS: Modifiable factors in the onset of AOM and OME episodes during the first 2 years of life include early age at colonization (</=3 months of age), day care outside the home, and not being breastfed.

Acute Disease↗