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David P Greenberg

Publications and source records attributed to David P Greenberg.

At least 19 recordsLinked to original sources
PubMed2006

Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.

CONTEXT: Chronic otitis media (OM) is a common pediatric infectious disease. Previous studies demonstrating that metabolically active bacteria exist in culture-negative pediatric middle-ear effusions and that experimental infection with Haemophilus influenzae in the chinchilla model of otitis media results in the formation of adherent mucosal biofilms suggest that chronic OM may result from a mucosal biofilm infection. OBJECTIVE: To test the hypothesis that chronic OM in humans is biofilm-related. DESIGN, SETTING, AND PATIENTS: Middle-ear mucosa (MEM) biopsy specimens were obtained from 26 children (mean age, 2.5 [range, 0.5-14] years) undergoing tympanostomy tube placement for treatment of otitis media with effusion (OME) and recurrent OM and were analyzed using microbiological culture, polymerase chain reaction (PCR)-based diagnostics, direct microscopic examination, fluorescence in situ hybridization, and immunostaining. Uninfected (control) MEM specimens were obtained from 3 children and 5 adults undergoing cochlear implantation. Patients were enrolled between February 2004 and April 2005 from a single US tertiary referral otolaryngology practice. MAIN OUTCOME MEASURES: Confocal laser scanning microscopic (CLSM) images were obtained from MEM biopsy specimens and were evaluated for biofilm morphology using generic stains and species-specific probes for H influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Effusions, when present, were evaluated by PCR and culture for evidence of pathogen-specific nucleic acid sequences and bacterial growth, respectively. RESULTS: Of the 26 children undergoing tympanostomy tube placement, 13 (50%) had OME, 20 (77%) had recurrent OM, and 7 (27%) had both diagnoses; 27 of 52 (52%) of the ears had effusions, 24 of 24 effusions were PCR-positive for at least 1 OM pathogen, and 6 (22%) of 27 effusions were culture-positive for any pathogen. Mucosal biofilms were visualized by CLSM on 46 (92%) of 50 MEM specimens from children with OME and recurrent OM using generic and pathogen-specific probes. Biofilms were not observed on 8 control MEM specimens obtained from the patients undergoing cochlear implantation. CONCLUSION: Direct detection of biofilms on MEM biopsy specimens from children with OME and recurrent OM supports the hypothesis that these chronic middle-ear disorders are biofilm-related.

Adolescent↗
PubMed2006

Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT).

BACKGROUND: Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. METHODS: This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. RESULTS: Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). CONCLUSIONS: Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.

Adolescent↗
PubMed2006

Characterization, distribution, and expression of novel genes among eight clinical isolates of Streptococcus pneumoniae.

Eight low-passage-number Streptococcus pneumoniae clinical isolates, each of a different serotype and a different multilocus sequence type, were obtained from pediatric participants in a pneumococcal vaccine trial. Comparative genomic analyses were performed with these strains and two S. pneumoniae reference strains. Individual genomic libraries were constructed for each of the eight clinical isolates, with an average insert size of approximately 1 kb. A total of 73,728 clones were picked for arraying, providing more than four times genomic coverage per strain. A subset of 4,793 clones were sequenced, for which homology searches revealed that 750 (15.6%) of the sequences were unique with respect to the TIGR4 reference genome and 263 (5.5%) clones were unrelated to any available streptococcal sequence. Hypothetical translations of the open reading frames identified within these novel sequences showed homologies to a variety of proteins, including bacterial virulence factors not previously identified in S. pneumoniae. The distribution and expression patterns of 58 of these novel sequences among the eight clinical isolates were analyzed by PCR- and reverse transcriptase PCR-based analyses, respectively. These unique sequences were nonuniformly distributed among the eight isolates, and transcription of these genes in planktonic cultures was detected in 81% (172/212) of their genic occurrences. All 58 novel sequences were transcribed in one or more of the clinical strains, suggesting that they all correspond to functional genes. Sixty-five percent (38/58) of these sequences were found in 50% or less of the clinical strains, indicating a significant degree of genomic plasticity among natural isolates.

Bacteriocins↗
PubMed2005

Efficacy of an acellular pertussis vaccine among adolescents and adults.

BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Adolescent↗
PubMed2005

A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy.

BACKGROUND: A phase 2 trial was conducted to assess in young infants the safety, tolerability, infectivity, and immunogenicity of multiple doses of an intranasal vaccine using bovine parainfluenza virus type 3 (bPIV3). METHODS: One hundred ninety-two healthy 2-month-old infants were randomized 1 : 1 : 1 to receive 1x10(5) median tissue culture infective dose (TCID(50)) bPIV3 vaccine, 1x10(6) TCID(50) bPIV3 vaccine, or placebo at 2, 4, 6, and 12-15 months of age. Safety information was collected by use of diary sheets and telephone interviews. Nasal wash and serum specimens were collected for assessment of infectivity and immunogenicity. RESULTS: The safety profiles of both dosages of bPIV3 were similar to that of placebo, with the exception of fever with temperature of >/=38.1 degrees C after dose 2 only, occurring in 34% of the 1x10(5) TCID(50) group, 35% of the 1x10(6) TCID(50) group, and 12% of the placebo group (P<.01). No vaccine-related serious adverse events were reported. The cumulative vaccine infectivity (isolation of bPIV3 and/or bPIV3 seroconversion) after dose 3 was similar in the 2 vaccine groups (87% in the 1x10(5) TCID(50) group and 77% in the 1x10(6) TCID(50) group) (P=.46). Seroconversion rates after dose 3, assessed by means of hemagglutination inhibition assay, after adjustment for decrease in maternal antibody titers, were 67% in the 1x10(5) TCID(50) group, 57% in the 1x10(6) TCID(50) group, and 12% in the placebo group (P<.01). Isolation of bPIV3 was common after dose 1, dose 2, or dose 3, but only 1 of 51 participants in the vaccine groups had bPIV3 isolated after dose 4. CONCLUSIONS: Multiple doses of bPIV3 vaccine were well tolerated and immunogenic in young infants.

Administration, Intranasal↗
PubMed2005

Parental perspectives on influenza immunization of children aged 6 to 23 months.

BACKGROUND: For the first time, in 2002, the Advisory Committee on Immunization Practices encouraged the vaccination of healthy children 6 to 23 months against influenza, whenever feasible. Participating inner-city health centers designed interventions to introduce influenza vaccination among this group of children. The study was designed to assess parents' attitudes toward the vaccine. METHODS: Following the 2002-2003 influenza vaccination season, parents were surveyed to identify barriers to and facilitators of influenza vaccination. A low-literacy level, 19-question survey was mailed to parents in three waves, 4 weeks apart. A subset of children had medical record data available to confirm vaccination status. Measures of validity were calculated. This paper focused only on the children whose parent-reported vaccination status was concordant with that reported in medical records (n = 193). Associations of responses to vaccination status were calculated in 2004, using chi-square and logistic regression procedures. RESULTS: Sensitivity was 85.7% and specificity was 66% (kappa = 0.50), assessing the ability of parents to recall receipt or nonreceipt of influenza vaccine. The most important factors related to immunization of healthy infants were perceived doctor's recommendation (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 2.4-12.3; p < 0.001) and belief that getting an influenza shot is a smart idea (OR = 3.5; 95% CI = 1.3-8.9; p < 0.01) for those with medical record-confirmed vaccination status. CONCLUSIONS: A clear message that the doctor recommends influenza vaccination for a child is an important factor for ensuring vaccination, and may foster the idea that vaccination is "smart."

Data Collection↗
PubMed2005

Penicillin susceptibility of pneumococcal isolates causing acute otitis media in children: seasonal variation.

BACKGROUND: During the past decade, the prevalence of nonsusceptible Streptococcus pneumoniae strains that cause acute otitis media (AOM) has increased to approximately 30%, and the proportion of fully resistant strains has also increased. The purpose of this study was to determine whether seasonal variation in resistance exists among pneumococcal isolates from children with AOM. METHODS: Between 1991 and 2003, children 2 months-8 years of age diagnosed with AOM according to stringent criteria underwent tympanocentesis in various clinical trials. RESULTS: Cultures from 567 of 794 tympanocenteses (71.4%) performed between 1991 and 2003 yielded AOM pathogens. During 1991-1995, only 1 of 43 S. pneumoniae isolates recovered (2%) was nonsusceptible to penicillin. The present analysis focuses on the 691 cultures obtained during 1996-2003; of these, 491 (71.1%) yielded AOM pathogens, of which 165 (33.6%) were S. pneumoniae. Of the pneumococcal isolates, 52 (31.5%) were nonsusceptible to penicillin. The proportion of nonsusceptible strains of S. pneumoniae increased over time: 0 of 3 (0%) in 1996; 2 of 11 (18%) in 1997; 14 of 40 (35%) in 1998; 3 of 34 (9%) in 1999; 11 of 25 (44%) in 2000; 11 of 22 (50%) in 2001; 4 of 18 (22%) in 2002; and 7 of 12 (58%) in 2003 (Cochran Armitage trend test, P = 0.03). AOM caused by nonsusceptible S. pneumoniae was more likely to occur as the winter progressed (P = 0.03); a similar trend was noted for the proportion of nonsusceptible strains that were fully resistant. CONCLUSIONS: In children with AOM, an increase in the proportion of episodes caused by nonsusceptible S. pneumoniae as the winter months progress may serve as a potential factor in guiding antimicrobial therapy for such children.

Child↗
PubMed2005

Health burden of pertussis in infants and children.

In countries with high rates of vaccination against pertussis, the incidence of this disease has decreased dramatically compared with the prevaccine era. However, pertussis still occurs in these countries, and severe morbidity and mortality are greatest among infants, particularly those who are unimmunized or incompletely immunized. Pertussis in older children and adults is perceived by many as being a mild disease, but it is a significant health burden in persons of all ages. Infants with pertussis experience the highest rates of hospitalization, complications and death. Severe complications include pneumonia, encephalopathy and meningoencephalitis. In addition, infants may experience weight loss, bronchitis, otitis media, apnea, cyanosis, inguinal hernia and rectal prolapse. It is essential to explore methods to prevent disease transmission to infants in the months before they complete their primary immunization series. The Global Pertussis Initiative was established to assess the true health burden of pertussis in infants and to suggest strategies to combat transmission and infection with Bordetella pertussis, which remains a significant public health concern.

Cause of Death↗
PubMed2005

Pertussis in adolescents: increasing incidence brings attention to the need for booster immunization of adolescents.

As a result of waning immunity and improved awareness, the reported incidence of pertussis is increasing among adolescents in the United States. Symptoms of pertussis are often mild and difficult to diagnose in adolescents, but these individuals can transmit the infection to schoolmates and family members, including high risk infants. Improvements in diagnosis and prevention of pertussis in adolescents are needed.

Adolescent↗
PubMed2005

Safety and immunogenicity of the American Academy of Pediatrics--recommended sequential pneumococcal conjugate and polysaccharide vaccine schedule in pediatric solid organ transplant recipients.

OBJECTIVE: Solid organ transplant recipients are at increased risk for invasive pneumococcal disease. The American Academy of Pediatrics recommends immunization with sequential pneumococcal vaccines for this group; however, data are lacking. Accordingly, this study was designed to evaluate the safety and immunogenicity of the recommended regimen. METHODS: Pediatric solid organ transplant recipients (n = 25) between 2 and 18 years of age who had not previously received 7-valent conjugate pneumococcal vaccine (PCV7) were enrolled. These patients received 2 doses of the PCV7 and a single dose of the 23-valent polysaccharide pneumococcal vaccine (23V). Each vaccine dose was given 2 months apart. Healthy age-matched controls (n = 23) were enrolled for comparison. Controls received a single dose of PCV7 followed 2 months later by a single dose of 23V. Antibody concentrations to serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were measured by enzyme-linked immunosorbent assay prevaccination, 2 months after each vaccine dose and 5 to 7 months after 23V. Local and systemic reactions to each vaccine dose were recorded. RESULTS: Systemic and injection-site reactions were comparable between the 2 groups. Significant rises in serotype-specific pneumococcal antibody geometric mean concentrations from prevaccination levels were observed in both groups; however, final antibody responses to serotypes 1, 4, 9V, 14, 18C, 19F, and 23F were significantly lower in solid organ transplant recipients compared with the control group. Antibody concentrations did not increase significantly among solid organ transplant patients after the second dose of PCV7. No additional increase in PCV7-associated serotype-specific antibody levels was observed after the 23V dose in both groups. Heart transplant recipients had lower antibody responses compared with liver transplant recipients. CONCLUSIONS: Although the pneumococcal vaccine regimen was safe and immunogenic among pediatric solid organ transplant recipients, the patients did not seem to benefit from the second dose of PCV7 or from the 23V dose given 2 months later. Additional studies are needed to determine the number of PCV7 doses and the interval between PCV7 and 23V to induce optimal responses.

Adolescent↗
PubMed2005

A combined diphtheria, tetanus, five-component acellular pertussis, poliovirus and Haemophilus influenzae type b vaccine.

Ideally, combination vaccines should not only be safe and effective, but also integrate smoothly into the vaccination schedule and provide advantages over the use of separately administered vaccines. Pentaceltrade mark (Sanofi Pasteur Ltd., Toronto, Canada), a combination vaccine first licensed in Canada and subsequently in other countries, is immunogenic against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b when administered at 2, 4, 6 and 15-18 months of age. In published studies, the safety, immunogenicity and effectiveness of this combination vaccine were comparable with those of separately administered vaccines, with the advantage of a simplified dosing schedule.

Adolescent↗
PubMed2004

Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults.

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

Adolescent↗
PubMed2004

Feasibility of influenza immunization for inner-city children aged 6 to 23 months.

BACKGROUND: Annual influenza-related hospitalization rates of children aged < 2 years in the United States are second only to those of the elderly. Yet no recommendations existed for vaccinating healthy children aged 6 to 23 months until 2002, when the Advisory Committee on Immunization Practices encouraged influenza vaccination for them. This study tested the feasibility of vaccinating 6- to 23-month-old children against influenza and assessed the effect on timely receipt of other vaccines. METHODS: A pre-post trial was used in urban health centers serving low-income children. Sites selected interventions from strategies proven to increase vaccination rates. Targeted patients were aged 6 to 23 months by November 30, 2002 (N = 1534). RESULTS: Influenza vaccination rates for the 2002-2003 intervention season improved significantly from 6.5% to 38.5% for the first dose (p < 0.001). Second-dose rates were significantly improved over preintervention (1.9% preintervention, 13.2% intervention), but lower than first-dose rates. Mean ages at vaccination for other recommended childhood vaccines did not differ or were significantly younger (measles, mumps, and rubella vaccine [MMR] and varicella) for children who received influenza vaccine versus those who did not. Moreover, a higher percentage of influenza-vaccinated than unvaccinated children received MMR, diphtheria, tetanus, pertussis vaccine 3 (DTaP3), inactivated poliovirus vaccine 2 (IPV2), and Haemophilus influenzae b (Hib2) vaccines within a 2-month grace period of the recommended age (p < 0.039), with no differences between groups for Hib1, DTaP1, IPV1, and varicella. CONCLUSIONS: With directed effort, it is possible to increase influenza vaccination at health centers serving low-income children. The addition of a two-dose vaccine was not associated with delayed receipt of other vaccines among these children.

Child Health Services↗
PubMed2003

Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial.

CONTEXT: Acute otitis media (AOM) frequently complicates influenza infection. Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years. OBJECTIVE: To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children's Hospital of Pittsburgh before the 1999-2000 (411 children) and 2000-2001 (375 children) respiratory seasons (defined as December 1 through March 31 of the respective following year). Children received influenza vaccine or placebo in a 2:1 ratio. The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season. INTERVENTION: Two doses (0.25 mL each) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart. MAIN OUTCOME MEASURES: Proportion of children who developed AOM, monthly occurrence rate of AOM, estimated proportion of time with middle ear effusion, and utilization of selected health care and related resources. RESULTS: Of the 66 children in the vaccine group from whom serum samples were collected, seroconversion against strains in the vaccine formulations developed in 88.6% to 96.8%, depending on the specific strain. The efficacy of the vaccine against culture-confirmed influenza was 66% (95% confidence interval [CI], 34%-82%) in 1999-2000 and -7% (95% CI, -247% to 67%) in 2000-2001; however, influenza attack rates differed between these 2 periods (in the placebo group, 15.9% and 3.3%, respectively). Compared with placebo, influenza vaccine did not reduce the proportion of children who had at least 1 episode of AOM during the respiratory season (in the first cohort: vaccine, 49.2% vs placebo, 52.2%; P =.56 ]; in the second cohort: vaccine, 55.8% vs placebo, 48.3%; P =.17). The vaccine also did not reduce the monthly rate of AOM; the estimated proportion of time with middle ear effusion; or the utilization of selected health care and related resources. There were also no differences between the vaccine and placebo groups regarding any of these outcomes during peak influenza periods. The vaccines administered to both cohorts of children were well tolerated. CONCLUSION: Administration of inactivated trivalent influenza vaccine to children aged 6 to 24 months did not reduce their burden of AOM or their utilization of selected health care and related resources.

Acute Disease↗
PubMed2003

Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants.

BACKGROUND: Streptococcus pneumoniae (Sp) is an important bacterial pathogen in children. Nasopharyngeal (NP) colonization of S. pneumoniae is necessary for person-to-person transmission and often precedes invasive disease. METHODS: NP carriage of Sp was studied in 49 infants following administration of a heptavalent pneumococcal conjugate vaccine (PCV) conjugated to the outer membrane protein of serogroup b Neisseria meningitidis (vaccine serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F). The vaccine was administered at 2, 4, 6, and 12 months of age and carriage rates were compared to a concurrent group of 32 infants not given PCV and evaluated over the first 15 months of life. RESULTS: Overall, Sp was isolated in 86/367 (23%) of NP cultures and 49% of infants. Serotype 23F was significantly less prevalent in the PCV group (1.9%) than the control group (16.1%) (P<0.05). Analysis of the proportion of children with prevalent carriage or acquisition of carriage did not differ between groups when evaluated by age or serotype. We noted, however, decreased acquisition and carriage in the vaccine group 1 month following the 12 month dose of PCV for vaccine serotypes (76 and 52% reduction, respectively), but this did not reach statistical significance (P=0.3). Adjustment for age, daycare and antibiotic use by multivariate modeling revealed no difference in carriage of vaccine containing serotypes or non-vaccine serotypes between groups. CONCLUSION: We did not show a significant effect of this heptavalent PCV on NP carriage. Further study of this issue, including a larger population size, is needed.

Bacterial Outer Membrane Proteins↗