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Biomedical subjects

K M Edwards

Publications and source records attributed to K M Edwards.

At least 19 recordsLinked to original sources
PubMed1997

Combination vaccines consisting of acellular pertussis vaccines.

Combination vaccines consisting of multiple vaccine antigens delivered in a single injection simplify vaccine administration. Combining multiple antigens into one injection, however, presupposes that the administration of multiple vaccines in combination will not reduce the safety and immunogenicity of the component vaccines. New generation vaccines seek to combine many more antigens from multiple, different pathogens, making them difficult to study in controlled, double blind, randomized clinical trials because of the number of study arms required for complete evaluation. Methods to simplify studies of combination vaccines include building on the framework of earlier studies to calculate sample size and reduce the number of control arms, standardizing serologic assays and assessment of adverse reactions and determining serologic correlates of protection to minimize the need for multiple efficacy studies and to facilitate evaluation of immunogenicity studies. Preliminary data indicate that immune responses to combination vaccines including diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus are comparable with those seen when the vaccines are administered separately. In contrast studies of combination vaccines that include Haemophilus influenzae type b Hib antigens show a diminished Hib antibody response, although the clinical relevance of this lowered antibody response has not yet been determined. Numerous small safety studies of combined vaccines have not found evidence of increased adverse reactions.

Clinical Trials as Topic↗
PubMed1997

Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough.

OBJECTIVE: To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough. METHODS: This was a case series consisting of a convenience sample of 65 patients > or = 18 years of age who presented with a chief complaint of a cough lasting > or = 2 weeks. Patients were treated in the ED of an urban university hospital. Patients with immunosuppression, lung disease, pneumonia, or a cough lasting > or = 3 months were excluded. Acute and convalescent sera were assayed for antibody to C. pneumoniae. Subjects with C. pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of > or = 16, or an IgG titer of > or = 512 were considered to have evidence of acute C. pneumoniae infection. RESULTS: Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C. pneumoniae infection. Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C. pneumoniae from those who did not have the disease. Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C. pneumoniae infection. CONCLUSIONS: C. pneumoniae infection appears to be associated with a persistent cough in ED patients. Clinicians should consider this organism when evaluating these patients. It is unclear whether antibiotic therapy is indicated for these patients. If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.

Adolescent↗
PubMed1997

Expression of an antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attenuates lethal activity in a murine model.

Isogeneic bacterial strains that differ only in the production of a single microbial factor have been invaluable in studying the pathogenesis of bacterial infections. The targeted, intentional inactivation of a gene encoding a potential virulence determinant generally requires homologous recombination to replace the gene with an inactivated allele. To determine whether the insertion and expression of a fragment of a bacterial gene in an antisense orientation could be used as a rapid alternative to allelic inactivation for producing paired isogeneic isolates, we inverted a 600-bp fragment of the Staphylococcus aureus gene encoding alpha-toxin, hla, behind its native promoter on an Escherichia coli-S. aureus shuttle vector. A transformant of an S. aureus strain carrying the antisense hla fragment produced antisense hla RNA and made 16-fold less alpha-toxin than either its parent or an isogeneic transformant containing vector DNA without hla. Also, intraperitoneal injection of 1.5 x 10(9) CFU of the antisense hla-containing transformant was significantly less lethal in a murine model than that of the parent (1 of 10 versus 7 of 10 mice expired [P < 0.02]) or the transformant without hla (1 of 10 versus 7 of 7 mice expired [P < 0.001]). We conclude that the expression of a fragment of hla in an antisense orientation in S. aureus on a plasmid vector reduces alpha-toxin production and the lethal activity of the strain in a murine model. The antisense strategy for creating isogeneic strains of bacteria may facilitate molecular investigations into the pathogenesis of infection. It also may be useful in creating novel live-attenuated strains of bacteria for use as vaccine candidates.

Animals↗
PubMed1997

Twenty years of outpatient respiratory syncytial virus infection: a framework for vaccine efficacy trials.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. METHODS: A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. RESULTS: Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. CONCLUSIONS: RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates.

Ambulatory Care Facilities↗
PubMed1997

Comparison of serological results in the NIAID Multicenter Acellular Pertussis Trial with recent efficacy trials.

Comparison of the serological results from the NIAID-funded Multicenter Acellular Pertussis Trial (MAPT) and the efficacy trials are complicated by differences in assay methods, immunization schedules, vaccine lots and populations immunized. In spite of these differences, serological results closely approximating those obtained in the MAPT were found for most or all of the assayed antibodies in the Mainz and Erlangen studies. Serological results for some of the antigens included in the vaccines used in the Italian and Stockholm trials were similar to the MAPT results, while significant differences were noted with other antigens. Differences in immunization schedules and serological assay methods made comparisons between MAPT and the Gothenburg and Senegal trials more difficult. Our understanding of the efficacy trial results, and our ability to apply those results to the U.S. population, would be enhanced markedly by simultaneous re-analysis of stored sera from MAPT and selected efficacy trials. This goal should be given priority by the study organizers and sponsors.

Clinical Trials as Topic↗
PubMed1996

Prevalence and incidence of adult pertussis in an urban population.

OBJECTIVES: To determine the prevalence of Bordetella pertussis infection among adults who have prolonged cough for 2 weeks or longer and to estimate the incidence of B pertussis infection in adults in a defined urban population. DESIGN: A prospective clinical study. SETTING: Kaiser Permanente, San Francisco (Calif) Medical Center. PARTICIPANTS: One hundred fifty-three referred and participating health plan members 18 years old or older with the complaint of cough persisting for 2 weeks or longer and 154 health plan members 18 years old or older with no cough for the past 3 months (controls) were enrolled. Medical records for an additional 100 patients randomly sampled from 676 patients 18 years old or older with an ambulatory diagnosis of cough (60 with prolonged cough) were also reviewed. MAIN OUTCOME MEASURES: Prevalence of adult pertussis as determined by enzyme-linked immunosorbent assay IgG antibody levels to pertussis toxin in individuals with prolonged cough for 2 weeks or longer and the incidence of adult pertussis in San Francisco Kaiser health plan members. RESULTS: The prevalence of adult pertussis was 12.4% of the participating referrals. The incidence of adult pertussis was estimated to be 176 cases per 100 000 person-years (95% confidence interval, 97 to 255 cases). CONCLUSIONS: Adult pertussis is a significantly greater public health threat than previously suspected. Booster doses of acellular pertussis vaccine after 7 years of age may be an effective approach to minimize transmission and infection.

Adult↗
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↗