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K M Edwards

Publications and source records attributed to K M Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1996

The seroepidemiology of Bordetella pertussis infections: a study of persons ages 1-65 years.

Although the incidence of Bordetella pertussis infections had decreased significantly since the introduction of widespread vaccination, an increase in the number of cases has occurred recently. In an attempt to define the seroepidemiology of pertussis in Nashville, antibody levels to pertussis toxin (PT) and filamentous hemagglutinin (FHA) were measured by ELISA in 585 serum samples from healthy 1- to 65-year-old subjects. Data were analyzed by smooth curve fitting and by comparison of trends in PT and FHA titers across age groups. The results demonstrated a peak in PT and FHA titers in the 4-6 year age group, concurrent with the administration of booster doses of diphtheria-tetanus toxoid-pertussis vaccine. A second larger peak was noted in the 13-17 year age group. These data suggest that pertussis infection is frequent during the adolescent years.

Adhesins, Bacterial↗
PubMed1996

The multicenter acellular pertussis trial: an overview.

A multicenter, randomized, double-blind study was undertaken in 2342 infants to evaluate the safety and immunogenicity of 13 acellular and 2 whole cell pertussis vaccines combined with diphtheria and tetanus toxoids. Vaccines were administered to infants at 2, 4, and 6 months of age. Sera were obtained before the first vaccination (age 2 months) and 1 month after the third vaccination (age 7 months). All of the acellular vaccines produced significant increases in antibody for included antigens; mean antibody levels often exceeded those obtained with the reference whole cell vaccine. The vaccines were well-tolerated. All acellular vaccines were associated with significantly fewer adverse reactions than the control whole cell vaccine.

Adhesins, Bacterial↗
PubMed1996

Interlaboratory study evaluating quantitation of antibodies to Haemophilus influenzae type b polysaccharide by enzyme-linked immunosorbent assay.

An interlaboratory study was conducted to determine whether an enzyme-linked immunosorbent assay (ELISA) with an antigen preparation composed of various-sized fragments of Haemophilus influenzae type b polysaccharide conjugated to human serum albumin could be standardized across laboratories and whether the ELISA-derived results from different laboratories are equivalent to those obtained by the standard radioactive antigen binding assay (RABA) for quantitation of anti-H, influenzae type b polysaccharide antibodies. Twenty coded human serum samples were quantitated by ELISA in 11 laboratories and by RABA in 5 laboratories. The mean RABA-derived values served as the basis for all comparisons. While the overall correspondence of antibody values between the two methods was good, significant differences were found among some of the 11 ELISA data sets and among the mean RABA values. Seven laboratories generated higher ELISA antibody values for low-titered sera. Four laboratories generated antibody concentrations that were not statistically different between the two assay methods. The results therefore indicate that the ELISA can tolerate substantial variations in protocol, such as the use of different plates and different antibody reagents, without affecting the quantitation of serum antibodies. However, attention should be focused on low-titered sera, as some assay conditions may yield spurious results. This ELISA is a serologic assay which can serve as an alternative to the RABA for quantitation of antibodies to H. influenzae type h polysaccharide.

Adult↗
PubMed1996

Cat scratch disease: detection of Bartonella henselae DNA in archival biopsies from patients with clinically, serologically, and histologically defined disease.

Serological and epidemiological studies suggest that Bartonella henselae is the etiological agent of cat scratch disease. We designed a study to detect B. henselae in archival biopsies by polymerase chain reaction amplification of the 16S rRNA gene followed by Southern blot hybridization. Forty-two histologically defined cat scratch disease biopsies and eighteen controls were selected for blinded analysis. After testing, charts were reviewed for clinical, immunological, and microbial evidence of infection. Results were correlated with duration of illness and antimicrobial therapy. B. henselae DNA was identified in 27 of 42 (64%) histologically defined patients and 23 of 34 (68%) patients defined both clinically and histologically. There were no false positives (0 of 18). A small subset (n = 14) had cat scratch disease serological tests performed. B. henselae was identified in 8 of 10 serologically positive patients. Polymerase chain reaction detected 50% of our DNA-positive cases (most of these early in the clinical course). Southern blotting of amplicons both doubled sensitivity (detecting patients > 4 weeks into illness) and confirmed B. henselae as the causative species. Our study strongly associates B. henselae with cat scratch disease, suggesting that it may be the most likely etiological agent in the majority of patients with cat scratch disease.

Adolescent↗
PubMed1995

Pertussis infection in adults with persistent cough.

OBJECTIVE: To determine the prevalence of Bordetella pertussis infection in adult patients with persistent cough. DESIGN: Prospective case series. SETTING: Urban university hospital emergency department. PATIENTS: Convenience sample of 75 patients aged 18 years or older with a cough lasting 2 weeks or longer. Serum specimens from 67 patients without respiratory complaints were used to develop reference values. INTERVENTIONS: In patients with cough, nasopharyngeal culture and direct fluorescent antibody testing for B pertussis were performed and serum samples were obtained at the first visit and 1 month later. Serum specimens were assayed for antibody to pertussis toxin (PT) and filamentous hemagglutinin (FHA). MAIN OUTCOME MEASURES: A subject with one or more of the following was defined as having a pertussis infection: a positive B pertussis culture result, a four-fold change in PT or FHA titer, and/or a single PT or FHA titer at least 2 SDs greater than the geometric mean of the control group. RESULTS: No subject tested culture positive for B pertussis. Sixteen (21%) (95% confidence interval [CI], 13% to 32%) of 75 subjects met the serologic criteria for pertussis infection; for 13 (81%; 95% CI, 54% to 96%) of the 16, the criteria were met by the initial serum specimen. In contrast, the geometric mean levels of antibody to PT and FHA for the remaining 59 subjects with cough did not differ from those of the control group. Clinical symptoms and the lymphocyte count did not differentiate patients with pertussis from those without the disease. CONCLUSION: Pertussis is a common cause of persistent cough in adults and should be considered in the differential diagnosis. Clinical symptoms, pertussis culture, direct fluorescent antibody testing, and lymphocytosis are of limited value in making the diagnosis.

Adult↗
PubMed1995

Interchangeability of conjugated Haemophilus influenzae type b vaccines in infants.

OBJECTIVE: To evaluate the safety and immunogenicity of two Haemophilus influenzae type b (Hib) conjugate vaccines when administered in serial combination. These vaccines consisted of Hib capsular polysaccharide polyribosyl-ribitol phosphate (PRP) conjugated to the meningococcal outer membrane protein (OMP) complex (PRP-OMP) and H influenzae oligosaccharide conjugated to a mutant toxin (CRM197) isolated from Corynebacterium diphtheriae (HbOC). DESIGN: Randomized, double-blind, clinical trial evaluating five Hib vaccination regimens. SETTING: Vaccine Treatment and Evaluation Units and affiliated private pediatric practices at Saint Louis (Mo) University, Vanderbilt University, Nashville, Tenn, and Baylor College of Medicine, Houston, Tex. PATIENTS: A total of 497 healthy 2-month-old infants scheduled to receive routine immunization. INTERVENTION: Participants received either PRP-OMP or HbOC given as recommended by the manufacturer, PRP-OMP at 2 and 6 months, HbOC at 2 months, then PRP-OMP at 4 and 6 months, or PRP-OMP at 2 months and then HbOC at 4 and 6 months. Unconjugated PRP was given at 15 months to evaluate priming. RESULTS: Geometric mean antibody concentrations differed significantly among the groups following the second and third immunizations of the primary series and following booster immunization with unconjugated PRP. On each occasion, the groups receiving serial combinations of PRP-OMP and HbOC achieved mean antibody concentrations that equalled or exceeded those of the groups receiving a single product. Adverse reactions did not vary by group. CONCLUSIONS: The studied sequential combinations of Hib vaccines were safe and at least as immunogenic as either vaccine alone.

Antibodies, Bacterial↗
PubMed1995

Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin.

OBJECTIVE: To determine the nasopharyngeal colonization rate of penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in young children, and to assess its relationship with the incidence of otitis media. DESIGN: Observational study in 215 children younger than 6 years of age who received care in the Vanderbilt Vaccine Clinic from September 1, 1992, to August 31, 1993. RESULTS: Of 842 nasopharyngeal cultures obtained, results for 44% of the cultures were positive for S. pneumoniae; 73% of the isolates were serotypes 6, 14, 19, or 23. Younger children had significantly higher rates of pneumococcal colonization than older children, with a peak at 1 year of age. By microdilution susceptibility testing, 37% of the cultures with positive results were intermediately or highly resistant to penicillin. Significantly more serotype 19 and 23 isolates were penicillin resistant than organisms of other serotypes. Children younger than 2 years of age had a twofold higher percentage of resistant isolates than those older than 2 years of age. A significant association was noted between nasopharyngeal carriage of S. pneumoniae and acute otitis media (p = 0.0002); however, the incidence of acute otitis media did not differ significantly between children colonized with penicillin-susceptible or penicillin-resistant strains. Unresolved otitis media was diagnosed more often in children who were colonized with resistant organisms than in children colonized with susceptible strains (p = 0.04). CONCLUSIONS: There was a high rate of nasopharyngeal carriage of penicillin-resistant S. pneumoniae in this population of young children. Nasopharyngeal colonization was associated with an increased incidence of acute otitis media, and penicillin resistance was associated with an increased incidence of unresolved otitis media.

Acute Disease↗
PubMed1995

Efficacy and safety of pneumococcal revaccination after splenectomy for trauma.

OBJECTIVE: To assess the outcome of patient education after splenectomy and vaccination and to determine the safety and efficacy of pneumococcal revaccination 2 or more years after primary vaccination. MAIN OUTCOME MEASURES: Titers to serotype no. 6 and no. 23 pneumococcus and cutaneous and systemic reaction to revaccination. RESULTS: A total of 112 consecutive postsplenectomy patients receiving pneumococcal vaccine were identified; 45 were contacted and offered revaccination; 24 patients demonstrated a lack of understanding of the postsplenectomy state (unaware of splenectomy n = 2, unaware of splenectomy risk n = 8, unaware of vaccine n = 23); 3 patients had infections requiring hospitalization (pneumonia, strep throat and tonsillitis, pneumonia and bacteremia); 40 patients agreed to revaccination, and 33 patients returned for follow-up titers; 16 of 33 (48%) demonstrated at least a two-fold increase in at least one titer. Only 15% described the revaccination as worse than a tetanus shot. CONCLUSIONS: (1) Despite physician-patient conversations, pamphlets, and Medic Alert bracelets, patient retention was poor. (2) All splenectomy patients should be revaccinated and reeducated between two and six years after splenectomy. (3) Revaccination after two years was well tolerated. (4) There were no fatal episodes of pneumococcal sepsis in over 200 patient years.

Adult↗
PubMed1995

Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease.

OBJECTIVE: To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. DESIGN: Prospective, controlled trial. SETTING: Referral clinic and hospitalized patients in a university medical center. PARTICIPANTS: Eighty patients with CSD and 57 healthy control subjects of similar age. MAIN OUTCOME MEASURES: The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. RESULTS: Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. CONCLUSION: Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD.

Adolescent↗
PubMed1995

Comparison of 13 acellular pertussis vaccines: overview and serologic response.

OBJECTIVE: To compare the immunogenicity of a licensed conventional whole-cell (WCL) and 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines that differed in source, method of manufacture, and included antigens; all vaccines included diphtheria and tetanus toxoids. METHODS: Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Sera were obtained before the first immunization and 1 month after the third immunization and were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxins. Chinese hamster ovary cell toxin neutralization assays were performed, and levels of agglutinating antibodies were determined. RESULTS: Of 2342 infants enrolled, 1942 contributed usable preimmunization and postimmunization serum specimens. Each vaccine produced significant increases in antibodies directed against the included antigens; postimmunization antibody titers differed significantly among the DTaP vaccines. For each evaluated antigen, the majority of DTaP vaccines produced antibody responses that equaled or exceeded those produced by WCL. For some antigens (eg, PT), mean antibody levels by vaccine correlated poorly with the quantity of antigen included in each vaccine; for others (eg., fimbriae), there was a close correlation. CONCLUSION: Although serologic correlates of pertussis immunity are not defined, it is clear that DTaP vaccines can stimulate immune responses that exceed those of licensed whole-cell vaccine with respect to the measured antibodies. Particularly for PT, immunogenicity seems to depend on factors in addition to antigen concentration, possibly including antigen derivation and formulation. No DTaP was most or least immunogenic with respect to all included antigens.

Antibodies, Bacterial↗
PubMed1995

Comparison of 13 acellular pertussis vaccines: adverse reactions.

OBJECTIVE: To compare the reactogenicity of a licensed conventional whole-cell (WCL) and 13 acellular pertussis vaccines that differed in the source, manufacture, and quantity of included antigens; all vaccines included diphtheria and tetanus toxoids. METHODS: Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Parents recorded the occurrence of fever, redness, swelling, pain, fussiness, drowsiness, anorexia, and use of antipyretics for 2 weeks after each inoculation; nurses interviewed parents on the third day and at each succeeding visit; long-term follow-up information was collected from parents and medical records 1 year after the third immunization. RESULTS: Of 2200 vaccinated infants, 2189 contributed reaction data after 6375 vaccinations. For every acellular vaccine, every monitored reaction except vomiting occurred at a significantly lower frequency and severity than was seen with WCL. The groups receiving acellular pertussis vaccines differed significantly with respect to redness, swelling, pain, and vomiting, but not with respect to fussiness, antipyretic use, drowsiness, or anorexia. CONCLUSION: Although there were differences among the acellular vaccines, none was consistently the most or least reactogenic; all were associated with substantially fewer and less severe adverse reactions than a standard commercial whole-cell vaccine. Selection of acellular vaccines for further development and for introduction into efficacy trials can give priority to assessments of immunogenicity and purity, with comparative reactogenicity a secondary consideration.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

A randomized comparison of reactogenicity and immunogenicity of two whole-cell pertussis vaccines.

OBJECTIVE: To compare prospectively the reactogenicity and immunogenicity of two licensed whole-cell pertussis vaccines. METHODS: We conducted a prospective, randomized, double-blinded assessment of two licensed whole-cell pertussis vaccines with diphtheria and tetanus toxoids that were included in a multicenter trial evaluating 13 acellular pertussis vaccines. Infants were immunized at 2, 4, and 6 months of age with a single lot of Lederle (309 infants) or Massachusetts Public Health Biologic Laboratories (MPHBL; 94 infants) vaccine. RESULTS: The group receiving the Lederle vaccine demonstrated significantly higher antibody titers to pertussis toxin by enzyme-linked immunosorbent assay (ELISA) and by the Chinese hamster ovary cell pertussis toxin neutralization assay, and to fimbrial antigens by ELISA, as well as higher mean agglutinin titers. In contrast, the group receiving the MPHBL vaccine demonstrated higher ELISA antibody levels to filamentous hemagglutinin and pertactin. Similar differences were observed in the proportions of vaccinees seroconverting to these antigens. Rates of systemic and local reactions were relatively low for both vaccines. Although the Lederle product had substantially lower reactogenicity in this study than previously reported for that vaccine, the MPHBL vaccine was significantly less reactogenic in nearly all clinical categories. CONCLUSION: The two whole-cell vaccines demonstrated statistically significant differences in postimmunization antibody levels to all six evaluated pertussis antigens. Whether these statistically significant differences in antibody levels have clinical relevance is not clear. Rates of nearly all local and systemic reactions were significantly lower among the MPHBL group than the Lederle group. Licensed whole-cell diphtheria-tetanus-pertussis vaccines produced by different manufacturers cannot be assumed to be similar in reactogenicity or immunogenicity.

Antibodies, Bacterial↗
PubMed1995

Description and evaluation of serologic assays used in a multicenter trial of acellular pertussis vaccines.

OBJECTIVE: To describe and evaluate the assays used to measure the antibody responses in infants to 13 experimental acellular pertussis vaccines and 2 licensed whole-cell pertussis vaccines. METHODS: During a 53-week period, preimmunization and postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and a mixture of type 2 and type 3 fimbriae by enzyme-linked immunosorbent assay (ELISA), for whole-cell agglutinins (AGG), and for pertussis toxin-neutralizing antibodies by the Chinese hamster ovary cell assay. All ELISA reagents were characterized to assure antigen and isotype specificity of the assays. Intralaboratory reproducibility and temporal stability were evaluated by analysis of results of control sera and by assessment of the response to the control whole-cell vaccine. Interlaboratory reproducibility was assessed by repeating the assays on preimmunization and postimmunization sera for 10% of the infants in a second laboratory. RESULTS: For control sera having antibody concentrations at least four times the minimum level of detection, the coefficients of variation within and between the ELISAs consistently were less than 20%. Trend analysis indicated that none of the assays drifted by more than 20% during the study period, and no significant drift was seen in the response to the control whole-cell vaccine. Results from the two laboratories correlated well; correlation coefficients were .93 or greater for the four ELISAs, .79 for the Chinese hamster ovary cell assay, and .82 for the AGG assay. For four of the six assays, there was either no difference or a modest (< 15%) difference in the geometric mean values for sera tested in both laboratories. Larger quantitative differences were observed for the AGG (45% difference) and pertactin (61% difference) assays. CONCLUSION: Assay reproducibility and stability indicate that the standardized methods can be transferred between laboratories, and that the results accrued during a 1-year period for the 15 vaccines can be compared.

Agglutination Tests↗
PubMed1995

Simultaneous administration of Haemophilus influenzae type b vaccine with acellular or whole-cell pertussis vaccine: effects on reactogenicity and immune responses to pertussis vaccines.

OBJECTIVE: To evaluate the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. METHODS: Enrollment of infants into a large multicenter study of the safety and immunogenicity of 13 DTaP and 2 DTP vaccines was partially completed when the first Hib vaccine, HbOC (Haemophilus b oligosaccharide conjugate vaccine), was licensed for use in infants. Thereafter, at each immunization most infants received HbOC simultaneously with DTaP (or DTP), administered in opposite thighs. Postvaccination geometric mean titers or concentrations (GMTs) of pertussis antibodies as measured by six different assays were compared pairwise among groups of infants receiving 0, 1, 2, or 3 simultaneous HbOC immunizations. The incidence of reactions was compared between infants who received only DTaP or DTP and those who received HbOC simultaneously. RESULTS: Comparison of postvaccination GMTs was possible among groups of infants receiving different numbers of simultaneous immunizations for 10 of the 13 DTaP and both DTP vaccines. Increased HbOC exposure had no consistent dose-response effect on antibody titers for DTaP or DTP vaccines in any assay. Significant differences between groups in postvaccination GMTs were observed with 4 DTaP vaccines in 1 to 2 assays each; the GMTs were higher with increasing HbOC exposure for 2 DTaP vaccines and lower for 2 others. There was no significant increase in reactions with simultaneous HbOC and DTaP immunization. CONCLUSIONS: Based on these retrospective analyses, there did not seem to be an interference in pertussis immunogenicity or alteration in reactogenicity associated with the simultaneous administration of HbOC and DTaP. These findings are encouraging with respect to the development of DTaP-Hib combination vaccines.

Bacterial Proteins↗