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K M Edwards

Publications and source records attributed to K M Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1993

Comparison of monovalent and trivalent live attenuated influenza vaccines in young children.

Fifty children, 6 months to 2 years of age, were vaccinated intranasally with a trivalent preparation containing 10(6) TCID50 each of H1N1 and H3N2 and 10(4) (n = 14) or 10(6) (n = 36) TCID50 of B live, attenuated, cold-adapted (ca) influenza strains. The same doses were administered as monovalent vaccines to 69 comparably aged children. Forty-five controls were given placebo. No clinically significant adverse reactions to vaccines were observed. Of children seronegative to H1N1 or H3N2, > or = 90% were infected by these vaccine strains. Trivalent vaccine containing 10(4) TCID50 of B infected only 27% of children seronegative to B (3/11), which was markedly reduced from the 88% infection rate (7/8) following monovalent B vaccine of the same dose (P = .02); increasing the B dose to 10(6) TCID50 increased the infection rate to 81% (21/26). Replication of ca influenza viruses in tissue culture matched vaccine responses. Trivalent ca influenza vaccines can be formulated that are safe and immunogenic in young children.

Animals↗
PubMed1993

Antibodies to Bordetella pertussis adenylate cyclase toxin in neonatal and maternal sera.

To investigate the high prevalence among infants of antibodies to Bordetella pertussis adenylate cyclase toxin (ACT), cord-blood sera were examined for antibodies to ACT, filamentous hemagglutinin (FHA) and pertussis toxin (PT) using immunoblot analysis. Antibodies reactive with ACT were the most prevalent in neonatal sera. Similar reactivity of IgG with ACT was found in each sample of a given neonatal-maternal pair, yet IgM reactive with ACT was virtually absent in neonatal sera, suggesting that antibodies to ACT are maternally derived. Antibodies to ACT might come from infection or childhood vaccination of the mothers since pertussis vaccines from all US manufacturers elicited antibodies to ACT in mice. Alternatively, these antibodies may have been elicited by a cross-reactive antigen such as Escherichia coli alpha-hemolysin, since all of the neonatal and maternal sera contained antibodies reactive with alpha-hemolysin.

Adenylate Cyclase Toxin↗
PubMed1992

Impact of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine.

OBJECTIVE: To assess whether serum antibody responses to diphtheria-tetanus-pertussis (DTP) vaccine were affected by coadministration of Haemophilus influenzae type b capsular polyribosylribitol phosphate polysaccharide-tetanus protein (PRP-T) conjugate vaccine when given to patients at 2, 4, and 6 months of age. DESIGN: Randomized, double-blind clinical trial. SETTING: Urban Santiago, Chile. PATIENTS: Healthy infants assembled from health centers. Two hundred seventy-eight (74%) of 375 eligible infants participated; 222, who complied with the complete protocol, constituted the primary group under analysis. INTERVENTIONS: One of three vaccine regimens was given to study participants at 2, 4, and 6 months of age, either DTP mixed in the same syringe as PRP-T (group 1); DTP and PRP-T given at separate injection sites (group 2); or DTP without PRP-T (group 3). PRIMARY OUTCOME MEASURES: Titers of serum antidiphtheria toxoid, antitetanus toxoid, and pertussis agglutinin antibodies were measured in blood samples taken from patients 2 months after each dose. RESULTS: Serum antidiphtheria toxoid and antitetanus toxoid responses showed no important depressions in the patients receiving PRP-T. In contrast, geometric mean titers (GMTs) of pertussis agglutinins, expressed as reciprocal serum dilutions, after both the second and third doses (GMT2, GMT3) were lowest in group 1 (GMT2 = 89; GMT3 = 1230), intermediate in group 2 (GMT2 = 123; GMT3 = 1995), and highest in group 3 (GMT2 = 210; GMT3 = 3090; P less than .05 for trend group 1 less than group 2 less than group 3 after each dose). Antipertussis toxin and antipertussis filamentous hemagglutinin antibody titers also were depressed in patients who received PRP-T. Follow-up of a subset at 18 months revealed an expected decline of pertussis agglutinin titers to near baseline levels in each group. CONCLUSIONS: Concurrent administration of PRP-T vaccine with DTP vaccine, either in the same syringe or at different sites, interfered with antipertussis responses to a primary series of immunizations. Although the clinical significance of this antagonism is uncertain, these data underscore the caution required in decisions to add new vaccines to existing immunization regimens.

Antibodies, Bacterial↗
PubMed1992

Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.

We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

Antibody Formation↗
PubMed1991

Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children.

A cold-adapted (ca) influenza B reassortant vaccine consisting of two genes encoding the hemagglutinin and neuraminidase from wild-type influenza B/Ann Arbor/1/86 virus and the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus was evaluated in 18 seropositive and 57 seronegative infants and children. The ca reassortant was infectious in seronegative vaccinees, with an estimated 50% human infectious dose of 10(2.5) TCID50. Nasal wash specimens from vaccinees retained the temperature-sensitive phenotype, indicating that the virus was phenotypically stable after replication in fully susceptible children. The vaccine was highly immunogenic in the seronegative vaccinees; 54% of the seropositive vaccinees also developed an increase in serum antibody. The ca vaccine was well tolerated, with only a mild increase in upper respiratory tract symptoms seen in the seronegative vaccinees. These studies indicate that the B/Ann Arbor/1/86 ca reassortant is safe, immunogenic, and phenotypically stable in infants and children.

Antibodies, Viral↗
PubMed1991

Booster response to acellular pertussis vaccine in children primed with acellular or whole cell vaccines.

Few data are available on the effect of a booster dose of acellular pertussis vaccine in children primed as infants with acellular vaccine. We administered acellular pertussis vaccine (ACV) at 19 months to children immunized in infancy with ACV or whole cell vaccine. Forty-one infants had been randomly assigned to receive either ACV or whole cell vaccine at 2, 4 and 6 months of age. Antibody titers to pertussis toxin and filamentous hemagglutinin were significantly higher in ACV than whole cell vaccine recipients at 7 months; at 15 months antibody to filamentous hemagglutinin (but not pertussis toxin) remained significantly higher among those receiving ACV. At 19 months all 41 children received an ACV booster. Local and systemic reactions were few and minor and were equally distributed between the two groups. All children responded to booster with significant increases in antibody; these increases tended to be greater for those having been primed with ACV. ACV booster immunization appears safe and immunogenic, regardless of the vaccine given for primary immunization.

Age Factors↗
PubMed1991

Identification and characterization of two nonessential regions of the rabbitpox virus genome involved in virulence.

We have developed a means to identify genes associated with particular aspects of virulence. By beginning with an avirulent deletion mutant of rabbitpox virus and systematically reintroducing overlapping segments of the deleted region, we have identified two regions of the viral genome associated with increased virulence in mice. Evaluation of illness has been aided by the exploitation of weight loss as an indicator of pathogenesis. One of the regions identified by this method contains several open reading frames and includes two previously described genes. A third, as yet undescribed, gene within this region potentially encodes a product related to the C5 protein of human complement. The second region of DNA associated with increased virulence is the HindIII M fragment, which contains only one complete open reading frame. Analysis of this previously unreported gene shows coding potential for a polypeptide of 254 amino acids (approximately 25 kDa) which is related to the C4 component of human complement. The elucidation of two new viral genes related to complement components, taken together with the recent report of the biological activity of a poxvirus-encoded complement-binding protein, suggests the importance of interactions of the virus with the complement system during a normal infection.

Amino Acid Sequence↗
PubMed1991

Differences in antibody response to whole-cell pertussis vaccines.

It has been assumed that whole-cell pertussis vaccines (WCVs) commercially distributed in the United States are of comparable immunogenicity, as all must comply with established standards for licensure. However, we have recently noted significant differences in antibody responses between groups of infants receiving the two WCVs commercially available in the United States. In separate studies performed concurrently under similar protocols at Vanderbilt and Johns Hopkins universities, infants were randomized to receive either an acellular pertussis vaccine or WCV. The acellular pertussis vaccine used at the two sites was identical, but the WCVs were from different manufacturers. Antibody responses to acellular pertussis vaccine did not differ between the two studies; responses to WCV differed dramatically, with infants receiving the Lederle WCV producing a 46-fold increase in antibody to pertussis toxin, compared with a 2.4-fold increase for infants receiving the Connaught WCV (P = .00003). Evaluation of other comparative data sets that were available provided further support for the conclusion that the two commercially available WCVs consistently differed in their ability to induce antibody to pertussis toxin. These findings have important implications for the design and interpretation of clinical trials comparing acellular and WCV products.

Adhesins, Bacterial↗
PubMed1991

Parapneumonic empyema in children: decortication hastens recovery in patients with severe pleural infections.

The medical records of 61 children 0 to 18 years of age treated for empyema complicating pneumonia from 1977 to 1989 were reviewed with attention to clinical presentation, bacteriology, treatment and outcome. Streptococcus pneumoniae was the most common infecting organism, followed by Staphylococcus aureus, other streptococcal species, anaerobes, Haemophilus influenzae type b, Pseudomonas aeruginosa, and Eikenella corrodens. No organisms were recovered in 39% of patients. Twelve patients were treated successfully with antibiotics and thoracentesis alone, 23 patients underwent close tube thoracostomy and 26 required decortication. A thickened pleural "peel," scoliosis and opacification of a hemithorax on chest radiograph, as well as low pleural pH and glucose concentration, were associated with a poor response to medical management. A scoring system was developed to define the severity of pleural disease. In patients with severe pleural infections, decortication allowed more rapid defervescence (2.2 vs. 6.5 days) and earlier hospital discharge (4.4 vs. 12.4 days) than did closed tube thoracostomy (P less than 0.001).

Adolescent↗
PubMed1990

Pertussis vaccines.

Concern over adverse reactions temporally associated with whole cell pertussis vaccine and advances in the understanding of the Bordetella pertussis organism have led to a new generation of more purified acellular vaccines. The biology of the pertussis organism, epidemiology of disease, vaccine development over the decades, and vaccine efficacy and adverse reaction data from whole cell and acellular vaccine trials are presented. Questions that remain to be answered before acellular vaccine replaces conventional vaccine are defined, and future studies addressing these questions are proposed.

Bordetella pertussis↗
PubMed1990

Natural history of pertussis antibody in the infant and effect on vaccine response.

To better characterize the transplacental transfer and persistence of pertussis antibodies and their role in the immune response to vaccine, concentrations of pertussis agglutinins and antibodies to lymphocytosis promoting factor (LPF) and filamentous hemagglutinin (FHA) were measured in three distinct groups of serum. Transplacental pertussis IgG antibody concentrations in newborns were found to be comparable to corresponding maternal concentrations and to decline with a half-life of approximately 6 weeks. By the age of 4 months, most infants had no detectable antibodies to LPF or FHA. Higher concentrations of maternally derived antibody to LPF were associated with a significantly weaker antibody response to conventional vaccine. In contrast, acellular vaccine stimulated superior antibody production, regardless of antecedent concentrations of antibody to LPF. The data support continuation of the current schedule of pertussis immunization and further efforts to develop an acellular vaccine for use in young infants.

Adult↗
PubMed1990

An outbreak of acute rheumatic fever in Tennessee.

From January, 1987, until July, 1988, a significant increase in newly diagnosed cases of acute rheumatic fever was noted at our hospital. In sharp contrast to the 3 cases seen in 1986, 14 cases were diagnosed in 1987 (a significant increase from 1985 to 1986, P = 0.001). In the first 6 months of 1988 an additional 12 new cases were diagnosed (a further significant increase from 1987, P = 0.02). No further cases were diagnosed between July, 1988, and September, 1989. The major clinical manifestations were carditis in 73%, polyarthritis in 58% and chorea in 31%. In 15 of 26 patients an antecedent illness which included pharyngitis was noted; the remainder of patients were asymptomatic. Group A beta-hemolytic streptococci were isolated from 13 of 19 children cultured. Isolates from two patients with acute rheumatic fever were submitted for M typing: one isolate was mucoid M18/T18; the other isolate was a mucoid nontypable strain. The demographic characteristics of the 26 patients agree with classic descriptions in that patients were more likely to be urban, to come from large families and to have low incomes; racial breakdown of the group mirrored the Tennessee pediatric population. These characteristics stand in contrast to reports of recent outbreaks which describe suburban high income patients. These data suggest that practitioners should be again aware of acute rheumatic fever and that aggressive identification and treatment of streptococcal pharyngitis should continue to be a relevant public health concern.

Acute Disease↗
PubMed1990

Diphtheria, tetanus, and pertussis immunizations in adults.

Although only few cases of diphtheria are reported annually in the United States, substantial numbers of adults have declining levels of protective serum antitoxin. A recent outbreak of diphtheria in Sweden emphasizes the importance of reimmunizing adults in diphtheria toxoid, included as part of routine use of tetanus/diphtheria toxoid. Tetanus is a completely preventable disease. Yet, most of the 60 to 100 annual cases of tetanus occur in older adults with no prior history of immunization. Tetanus immunization should be a routine part of medical care of all adults. Research currently is aimed at improving the efficacy and safety of pertussis vaccine. Future vaccines may be useful in protecting health care workers and other adults who have extensive contact with children against pertussis.

Adult↗
PubMed1989

Antibiotic therapy for cat-scratch disease?

Cat-scratch disease is usually a benign, self-limited disease that causes regional lymphadenopathy. Occasionally, it may present with systemic symptoms and have a prolonged course. To date, antibiotic therapy has not been proved to be of value. We describe three patients with cat-scratch disease who were treated successfully with gentamicin sulfate. Two patients had extensive hepatic involvement, and one patient had regional lymphadenopathy. All three patients responded within 48 hours to intravenous gentamicin. Extensive follow-up has shown no recurrence of symptoms. These cases suggest that gentamicin may be efficacious in shortening the course of cat-scratch disease. Prospective, randomized trials should be performed to confirm these results.

Cat-Scratch Disease↗
PubMed1989

Immunization after invasive Haemophilus influenzae type b disease. Serologic response to a conjugate vaccine.

Fifteen children with previous invasive Haemophilus influenzae type b disease were immunized with a Hemophilus-diphtheria toxin mutant protein conjugate vaccine. Serologic responses were compared with those of 31 newly immunized children without previous invasive H influenzae type b disease. Mean levels of antibody to polyribosylribitol phosphate among study children younger than 18 months were 0.086 mg/L before immunization, 0.737 mg/L after first immunization, and 4.453 mg/L after second immunization. In contrast, the comparable mean polyribosylribitol phosphate antibody levels among control children younger than 18 months were 0.107, 3.580, and 63.502 mg/L. A similar pattern of results was found among children aged 18 months or older. Although children with previous invasive H influenzae type b disease do not respond as vigorously to conjugate vaccine as do previously healthy controls, the response is sufficient to justify routine immunization of such children.

Age Factors↗
PubMed1989

Evaluation of a new highly purified pertussis vaccine in infants and children.

Purified acellular pertussis vaccine (12.5 micrograms of lymphocytosis promoting factor [LPF] and 12.5 micrograms of filamentous hemagglutinin [FHA]) was compared with conventional pertussis vaccine in a randomized double-blind study involving 40 children aged 4-6 y, 40 children aged 18-24 mo, and 50 infants. Increases in antibody were significantly greater among recipients of acellular vaccine than among recipients of conventional vaccine for antibodies to LPF in all age groups and for antibodies to FHA in infants and children aged 4-6 y; the increase in FHA antibody was also greater with acellular vaccine among children aged 18-24 mo but not significantly so. Compared with conventional vaccine, acellular vaccine was significantly associated with reduced frequency of leg pain and fretfulness at all ages and less frequent fever and anorexia at some ages. The reduced reaction rates and comparable or enhanced immunogenicity of the acellular vaccine make it an attractive candidate for larger field trials, particularly among infants.

Antibodies, Bacterial↗
PubMed1989

PFAPA syndrome.

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Child, Preschool↗