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Biomedical subjects

H Faden

Publications and source records attributed to H Faden.

At least 37 records · Page 2Linked to original sources

Adherence of nontypeable Haemophilus influenzae to respiratory epithelium of otitis-prone and normal children.

Three hundred six children were enrolled at birth in a prospective study of otitis media and followed up for 2 years. Adherence of nontypeable Haemophilus influenzae to buccal epithelial cells was compared between otitis-prone children and age- and sex-matched normal controls at birth, 1 year, and 2 years. The mean +/- SD/median percent adherence was similar for the two groups at birth (1.6 +/- 2.3/1.0 versus 1.2 +/- 1.4/1.0; NS) and at 2 years (1.6 +/- 1.7/1.5 versus 2.1 +/- 2.1/1.5; NS). At 1 year of age the adherence rate for the otitis-prone group (2.4 +/- 2.6/1.0) was statistically greater than that for the control group (1.0 +/- 1.3/0.0; p < .02). Because this difference is probably clinically insignificant, other explanations must be sought for the increased colonization rates of nontypeable H influenzae observed in otitis-prone children.

Bacterial Adhesion↗

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first two years of life.

A total of 200 children were followed from birth through 2 years of age with nasopharyngeal (NP) cultures to determine the normal colonization pattern of nontypeable H. influenzae (NTHI) in young children. NP cultures were obtained routinely at 13 scheduled visits. 44% of children became colonized by 2 years; acquisition was greatest in the first year. Colonization with the initial strain, as determined by outer membrane proteins, persisted from 1-5 months, median 2 months. Children carried one predominant strain at a time but became colonized with up to 7 different strains, mean 2.2, over 2 years. Three patterns of colonization were observed: i) rapid elimination of the initial strain, ii) prolonged colonization with the initial strain, and iii) colonization with different strains. Reacquisition of a previously carried strain was rare. Changes in outer membrane protein patterns reflected acquisition of new strains rather than phenotypic changes of old strains. Children colonized with 1 strain for < or = 2 months generated a greater mucosal antibody response, log 2.35, U/ng/ml SIgA, than children colonized with different strains, log 1.89, U/ng/ml SIgA, p <0.01. These data suggest that duration of colonization with one strain and the acquisition of a new strain is regulated by the local specific SIgA.

Bacterial Outer Membrane Proteins↗

Adherence of nontypable Haemophilus influenzae to respiratory epithelium of otitis prone and normal children.

The present study was designed to determine whether nontypable H. influenzae adhered differently to buccal cells from otitis prone compared with normal children. 306 children were enrolled at birth. They were examined at 1-6, 8, 10, 12, 15, 18, 21, and 24 months of age. Buccal cells were collected at 1, 12, and 24 months. 40 children were classified as OP (> or = 4 episodes by age 12 months or > or = 6 episodes by age 24 months). Adherence assays were conducted by incubating 1 x 10(4) buccal cells with 5 x 10(8) colony forming units of radiolabelled nontypable H. influenzae in 1 ml of salt solution with 0.1% gel at 37 degrees C for 60 min. Adherence was expressed as the % of organisms adherent to buccal cells. The adherence of buccal cells from otitis prone children were compared with age and sex matched controls who had not experienced otitis media and had not been colonized with nontypable H. influenzae.

Breast Feeding↗

Adenoid lymphocyte responses to outer membrane protein P6 of nontypable Haemophilus influenzae in children with and without otitis media.

The cellular immune responses to nontypable Haemophilus influenzae in adenoids were determined in children by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. In the lymphocyte transformation assay, stimulation index of adenoid lymphocytes stimulated by P6 in otitis children (2.34 +/- 0.25) was significantly lower than that in non-otitis children (3.91 +/- 0.64, p <0.05). The number of IgM as well as IgA secreting cells after 8 days' culture with P6 were significantly smaller in otitis children (IgM: 7,534 +/- 2,843/10(6) lymphocyte; IgA: 1,573 +/- 620/10(6) lymphocyte) than those in non-otitis children (IgM: 12,994 +/- 2,533, p <0.05; IgA: 2,828 +/- 528, p <0.05). These data suggest that P6 protein is a target for the cellular immune response of the adenoid, and failure of adenoid lymphocytes to recognize it as a specific immunogen may be one of the causes of recurrent otitis media.

Adenoids↗

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life.

Two hundred children were followed from birth through 2 years of age with nasopharyngeal cultures to determine the normal colonization pattern of nontypeable Haemophilus influenzae. Forty-four percent of the children were colonized on one or more occasions; the acquisition rate was greatest in the first year. Monthly prevalence rates were 11%. Colonization with the initial strain persisted 1-5 months (median, 2). Children carried 1 predominant strain at a time but became colonized with up to 7 different strains (mean, 2.2). Children colonized with a single strain for < or = 2 months produced a greater nasopharyngeal secretory IgA to nontypeable H. influenzae response than did children colonized with different strains (log 2.35 +/- 0.68 vs. 1.89 +/- 0.25 U of P6 secretory IgA/ng/mL of total secretory IgA, P < .01). The duration of colonization with a strain and acquisition of a new strain may be affected in part by the local production of specific secretory IgA.

Aging↗

Cellular immunity to the P6 outer membrane protein of nontypeable Haemophilus influenzae.

Cellular immunity to nontypeable Haemophilus influenzae in a population of 10 healthy, immune adults was determined by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. P6 (200 microliters/ml) induced lymphocyte blast transformation that peaked on day 10 of incubation. The peak induction of antibody-secreting cells occurred on day 8 of incubation. In comparison with the response to tetanus toxoid stimulation, the peak lymphocyte blast transformation response to P6 was reduced (mean counts per minute +/- standard error of the mean [SEM], 3,457 +/- 503 versus 9,414 +/- 1,464; P = 0.0051) and delayed (mean days +/- SEM, 10.3 +/- 0.4 versus 8.4 +/- 0.5; P = 0.0169); however, P6 was a better stimulus of antibody secretion from lymphocytes, particularly antibody of the immunoglobulin M (IgM) class (mean peak numbers of antibody-secreting cells per 10(5) peripheral blood mononuclear cells +/- SEM: IgG, 85 +/- 29 versus 42 +/- 16 [P = 0.0469]; IgM, 81 +/- 20 versus 25 +/- 7 [P = 0.0125]; IgA, 24 +/- 8 versus 16 +/- 6 [P = 0.0526]). Thus, lymphocytes from immune individuals recognize P6 of nontypeable H. influenzae as an immunogen. These data provide a basis for future studies with otitis-prone children who fail to develop a normal antibody response to P6 antigen (N. Yamanaka and H. Faden, J. Pediatr. 122:212-218, 1993).

Adult↗

Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization.

Sixty-eight children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk antibody on nasopharyngeal colonization. Human milk secretory IgA antibody to P6, a highly conserved outer membrane protein of nontypeable Haemophilus influenzae, was measured with the use of an enzyme-linked immunosorbent assay. Nasopharyngeal colonization with nontypeable H. influenzae and the occurrence of otitis media were determined. Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%) had otitis media. Frequency of isolation of nontypeable H. influenzae was directly related to episodes of otitis media (r = 0.35; p = 0.001). The level of human milk anti-P6 secretory IgA antibody was inversely related to frequency of isolation of the organism (r = -0.27; p = 0.026). The average antibody level, expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to children with no colonization of nontypeable H. influenzae was significantly higher than in milk fed to children in whom colonization occurred on multiple occasions (156 +/- 120 vs 69 +/- 50; p = 0.013). Prevention of colonization was most evident during breast-feeding. These data suggest that the protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with nontypeable H. influenzae by specific secretory IgA antibody.

Acute Disease↗

Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media.

Nasopharyngeal colonization with Moraxella catarrhalis was evaluated in a large cohort of infants followed prospectively from birth to 2 years of age; 120 children were examined at 13 routine visits. Of these, 66% became colonized with M. catarrhalis by 1 year and 77.5% by 2 years. Nasopharyngeal colonization with M. catarrhalis increased from 27.0% during healthy visits to 62.7% during visits due to otitis media (P < .001). Otitis-prone children were colonized at 44.4% of all visits compared with 16.7% for children who did not have otitis media (P < .001). DNA from 112 strains of M. catarrhalis from 34 children were evaluated; 106 were successfully digested with restriction enzymes and demonstrated a great degree of heterogeneity. Children tended to acquire and eliminate a number of different strains. Intrafamilial spread of the same strain of M. catarrhalis was frequent. These data suggest that nasopharyngeal colonization with M. catarrhalis is common throughout infancy. A high rate of colonization is associated with an increased risk of otitis media.

Child, Preschool↗

Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics.

The relationship between nasopharyngeal colonization with nontypeable H. influenzae and recurrent otitis media was assessed in 157 children followed prospectively from birth through 12 months of age. Forty-nine (31%) became colonized. Nasopharyngeal secretory IgA (sIgA) reactive with the P6 outer membrane protein was detected in all colonized children. Reduction or elimination of the organism was associated with a better mucosal immune response (560 +/- 864 units/ng/mL of sIgA) than was persistence in the nasopharynx (121 +/- 81; P = .04). Forty colonized children (82%) and 61 noncolonized children (56%) developed otitis media (P = .004); colonized children were four times more likely to be classified as otitis prone (P = .003). The frequency of otitis media episodes was directly related to the frequency of colonization (r = .42, P < .01). These results demonstrate a strong relationship between nasopharyngeal colonization patterns and otitis media. The mucosal immune response may be important in elimination of potential pathogens from the respiratory tract.

Age Factors↗

Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media.

Antimicrobial susceptibility was determined for strains of Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis recovered from the nasopharynxes of children followed from birth. The bacteria tested were the first potential pathogens isolated from each child before any treatment with antibiotics. Minimal inhibitory concentrations of commonly used oral antibiotics demonstrated the following overall rates of resistance for (1) S. pneumoniae: penicillin 1.2% (intermediate susceptibility 4.8%), trimethoprim-sulfamethoxazole 20%; (2) nontypable H. influenzae: ampicillin 32%, cefaclor 17%; (3) M. catarrhalis: ampicillin 90%, trimethoprim-sulfamethoxazole 19%. Antibiotic regimens used for treatment of otitis media may have to be evaluated in light of changing antibiotic susceptibilities.

Anti-Bacterial Agents↗

Immune response to Moraxella catarrhalis in children with otitis media: opsonophagocytosis with antigen-coated latex beads.

Opsonic antibody activity against Moraxella catarrhalis was determined in sera from children with otitis media. The antibody was determined with a new assay utilizing outer membrane antigen-coated latex beads. Antigen-coated beads opsonized in heat-inactivated pooled human serum phagocytosed 47.5 +/- 36.1 beads per 100 neutrophils compared to 15.6 +/- 10.2 beads per 100 neutrophils opsonized in hypogammaglobulinemic serum (p < .025). Antigen-coated beads opsonized in homologous sera from 11 children with M. catarrhalis otitis media demonstrated increased opsonic activity in convalescent sera (34.6 +/- 27.1) compared to acute sera (15.5 +/- 6.7; p < .05). These data suggest that infection with M catarrhalis is associated with the development of opsonic antibody.

Antigens, Bacterial↗

Antibody response to outer membrane protein of nontypeable Haemophilus influenzae in otitis-prone children.

One of the major outer membrane proteins of nontypeable Haemophilus influenzae, P6, is highly conserved among strains, serves as a target for bactericidal antibody, and has been proposed as a possible vaccine candidate. The serum antibody response to P6 was studied in otitis-prone and normal children by an enzyme-linked immunosorbent assay. Of 20 otitis-prone children, 12 (60%) had a serum IgG antibody response to P6 after otitis media; however, the mean acute antibody level for the group, 4.6 micrograms/ml, was not significantly different from the convalescent level, 5.4 micrograms/ml. Anti-P6 antibody levels were also measured longitudinally for 10 to 25 months in 30 otitis-prone and 13 healthy children. Antibody levels increased sevenfold in the normal group compared with less than three-fold for the otitis-prone group and were significantly higher in the normal children after the age of 18 months (p < 0.05). Finally, otitis-prone children who had two or more episodes of otitis media with nontypeable H. influenzae did not have an anamnestic antibody response to P6. The failure to recognize P6 as a specific immunogen may account for recurrent infections. Moreover, the data suggest that otitis-prone children may not respond adequately to a vaccine containing P6.

Antibodies, Bacterial↗

Poliovirus vaccination: a trilogy.

The incidence of poliomyelitis has declined dramatically since the introduction and widespread use of inactivated (IPV) and live oral (OPV) poliovirus vaccines. In the United States, fewer than 10 cases of paralytic poliomyelitis are reported each year, and all cases are vaccine associated. In contrast, paralytic disease due to wild virus continues to be a problem in less developed nations, in part due to poor seroconversion rates after receipt of OPV. The recent introduction of enhanced potency IPV has stimulated the prospects for a combined vaccine schedule that will reduce the frequency of vaccine-associated paralytic polio and retain good mucosal protection. Recent studies suggest that two doses of enhanced potency IPV followed by two doses of OPV provide excellent systemic and local immunity against polioviruses 1, 2, and 3.

Antibodies, Viral↗

Long-term immunity to poliovirus in children immunized with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines.

Eighty-six children who completed immunization with the two trivalent poliovirus vaccines, live attenuated (OPV) and enhanced potency inactivated (EIPV), in one of four schedules (OPV-OPV-OPV, EIPV-EIPV-EIPV, EIPV-OPV-OPV, and EIPV-EIPV-OPV) at 1 year of age were monitored serologically over the subsequent 4 years and challenged with OPV at 5 years of age. Each of the immunization groups exhibited an initial 10- to 100-fold decline in neutralizing antibody to poliovirus types 1, 2, and 3 during the first 2 years of follow-up; thereafter antibody titers stabilized. The EIPV-EIPV-OPV group maintained the highest antibody levels throughout the observation period, including the response to OPV challenge at 5 years of age. These data suggest that immunization with OPV, EIPV, and combinations of the two vaccines confers long-term immunity. Optimal systemic immunity was associated with two or more doses of EIPV.

Antibodies, Viral↗

Local antibody response to P6 of nontypable Haemophilus influenzae in otitis-prone and normal children.

The local antibody response to the outer membrane protein, P6, of nontypable H. influenzae was measured in middle ear fluids of 30 children during 46 episodes of otitis media, and in nasopharyngeal secretions from 7 children evaluated on 18 occasions. Immunoglobulin G antibody to P6 was detected in 92% of middle ear fluid compared to 70% for IgM, 78% for IgA, and 45% for secretory IgA. Antibody levels ranged from a high of 249 ng/ml for IgG to a low of 11 ng/ml for IgM. Concentrations of P6 specific IgG in the middle ear fluid was directly related to the concentration in the serum, r = 0.89, p < 0.001, and inversely related to the number of bacteria present, r = -0.62, p < 0.05. In contrast, IgA and secretory IgA antibodies to P6 were common (96% and 95%, respectively) and in relatively high concentrations (33 ng/ml and 29 ng/ml, respectively) in nasopharyngeal secretions. There was no relationship between nasopharyngeal and serum levels of antibodies. These data suggest that antibody to P6 nontypable H. influenzae is common, diffuses into the middle ear spaces passively from the serum during otitis media, and is manufactured locally in the nasopharynx in response to colonization.

Antibodies, Bacterial↗