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Biomedical subjects

R S Daum

Publications and source records attributed to R S Daum.

At least 55 records · Page 3Linked to original sources

Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period.

OBJECTIVE: To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. DESIGN: Randomized clinical trial. SETTING: Suburban New Orleans pediatric population. PARTICIPANTS: Convenience sample of 150 healthy infants. METHODS: Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. RESULTS: The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). CONCLUSIONS: Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

Antibodies, Bacterial↗

Nosocomial epiglottitis associated with penicillin- and cephalosporin-resistant Streptococcus pneumoniae bacteremia.

We cared for a 4-year-old male with nosocomially acquired epiglottitis caused by Streptococcus pneumoniae. He had been receiving ceftazidime therapy when this infection was recognized. The S. pneumoniae isolate was of serotype 15B and was resistant to beta-lactam antibiotics, cephalosporins (including those with extended spectra), and trimethoprim-sulfamethoxazole. Clinicians and clinical microbiologists must be aware that cephalosporin susceptibility may no longer be assumed for penicillin-resistant S. pneumoniae isolates and that susceptibility testing for the extended-spectrum cephalosporins should be performed whenever this species is isolated from a normally sterile body fluid.

Bacteremia↗

Accuracy of immunization histories provided by adults accompanying preschool children to a pediatric emergency department.

OBJECTIVE: Because some have advocated the use of emergency departments to administer delayed childhood immunizations, we evaluated the accuracy of immunization histories obtained in this setting by comparison with medical records of inner-city health care facilities. DESIGN: Questionnaires were orally administered to adults accompanying children to the emergency department. Individual medical records were reviewed. SETTING: Pediatric emergency department at Wyler Children's Hospital, University of Chicago and 68 inner-city primary care clinics. PATIENTS: Children aged 3 to 65 months registering for medical care. Of the sample, 98% were African American; 75% were Medicaid recipients. MAIN OUTCOME MEASURES: Adults' knowledge of immunization histories, immunization cards, and medical records compared with American Academy of Pediatrics/Immunization Practices Advisory Committee recommendations. RESULTS: Of the accompanying adults, 64% stated that their child's general immunization status was "up-to-date"; 65% of these had clinic records confirming that status. Only 8% of specific regimens stated by these adults accurately matched those found in clinic records. Moreover, 45% of adults accompanying children at least 16 months and older provided inaccurate information regarding previous receipt of measles immunization. CONCLUSION: Information provided by accompanying adults (from recall or from immunization cards) is inadequate to determine accurately which preschoolers in the pediatric emergency department are delayed in immunizations.

Chicago↗

Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses.

The Haemophilus influenzae capsular polysaccharide-outer membrane protein conjugate, PRP-OMPC (PedvaxHIB) elicits very good antibody responses in infants > or = 2 months of age after the first dose. Increasing age at time of first vaccination correlates with higher antibody responses. Anti-PRP responses are consistently high with the first injection among all population groups studied. Booster doses stimulate anamnestic antibody responses after one year of age. Among US children (excluding Navajo and Apache children) given a primary injection at 14-18 months of age, the geometric mean titre (GMT) after 2 to 3 years was > 1 micrograms/ml. US children (excluding Navajo and Apache children) given a primary series at 2 and 4 months of age and a booster at 18 months of age also had an anti-PRP GMT > 1 micrograms/ml 2.5 years later. Navajo and Apache children given a primary series at 2 and 4 months of age and a booster at 12-15 months had antibody levels of 1.50 micrograms/ml one year later. Antibody persistence data suggest there will be long-term protection against Haemophilus influenzae b disease following immunization with PRP-OMPC.

Antibodies, Bacterial↗

Severe measles in immunocompromised patients.

OBJECTIVE: To describe the severity of measles in immunocompromised hosts and to assess preventive and therapeutic modalities. DATA SOURCES: Patients admitted to two academic medical centers between September 1989 and December 1990 and English language references obtained by MEDLINE from 1963 to 1991. Bibliographies were used to identify reports prior to 1963. STUDY SELECTION: We identified nine immunocompromised patients with measles. Further analysis was based on 35 patients from two cohort studies of measles in oncology patients and 24 reported cases of measles in human immunodeficiency virus (HIV)-infected patients. DATA EXTRACTION: Clinical data are presented from the nine patients we treated. Information concerning measles complications, presence of rash, use of prophylactic immunoglobulin, and therapeutic measures was extracted from the literature. DATA SYNTHESIS: Of our nine patients, eight developed severe complications and two died. Two patients had no rash. In combining our patients with those from the literature, severe complications occurred in about 80%. The case fatality rate for severe measles was about 70% for oncology patients and about 40% for HIV-infected patients. Rash was absent in about 30%. The efficacy of prophylactic or therapeutic measures could not be assessed due to the small number of patients. However, we observed a rapid defervescence following administration of ribavirin. Vaccinated, HIV-infected patients had a lower mortality rate than those not previously vaccinated (P = .06). CONCLUSIONS: Measles is a severe illness in immunocompromised patients, and the absence of rash is frequent. While treatment is supportive, ribavirin requires further study. Measles vaccine may be efficacious in HIV-infected patients. Vaccination of oncology patients should be reassessed.

Adolescent↗

Characterization of Staphylococcus aureus isolates with decreased susceptibility to vancomycin and teicoplanin: isolation and purification of a constitutively produced protein associated with decreased susceptibility.

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Bacterial Proteins↗

IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants.

PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC.

Antibodies, Bacterial↗

Occurrence and mechanisms of glycopeptide resistance in gram-positive cocci.

Despite belief that the unique mechanism of glycopeptide action would preclude the development of resistance in susceptible organisms, clinical isolates of enterococci and staphylococci resistant to these compounds have been described. Among the enterococci, there are at least three types of resistance. Type A (high-level) resistance was described in Enterococcus faecium and E. faecalis. It is inducible and mediated by elaboration and/or increased activity of at least three enzymes: a ligase, a dehydrogenase, and a carboxypeptidase, which orchestrate the production of peptidoglycan precursors that do not bind vancomycin. Type B (low-level) resistance described in E. faecium is also mediated by increased carboxypeptidase activity and, possibly, by elaboration of a protein detectable after incubation in vancomycin whose function is unknown. Type C resistance is associated with production of a ligase constitutively produced, chromosomally encoded, and unique to E. gallinarum. Among the staphylococci, coagulase-negative clinical isolates were obtained that were resistant to glycopeptides and one coagulase-positive isolate was resistant to teicoplanin but the mechanism of resistance is unknown. Additionally, coagulase-positive staphylococci resistant to glycopeptides have been prepared in the laboratory. They produce an approximately 39-kDa cytoplasmic protein, whose function is unknown, and have undergone extensive reorganization of their cell surface. The era in which universal gram-positive susceptibility to glycopeptides can be presumed is over; susceptibility testing must now accompany isolation of an enterococcus or staphylococcus of clinical importance.

Amino Acid Sequence↗

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants. The APDT Vaccine Study Group.

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

Agglutination Tests↗

Successful medical treatment of presumed Candida endocarditis in critically ill infants.

Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants.

Amphotericin B↗

Serum anticapsular antibody response in the first week after immunization of adults and infants with the Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine.

Eight healthy adults and 48 infants 2 and 4 months old were immunized with Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMP) to evaluate antibody kinetics in the first days after immunization. Five adults (63%) had some decrease in antibody, although the geometric mean did not decrease significantly. With one exception, the nadir occurred on postimmunization day 3. Seven had an antibody increase by day 7. Of the children, 6 (75%) of 8 and 17 (77%) of 23 had a decrease in antibody in serum obtained on day 2-3 after the first or second dose, respectively, the magnitude of which directly correlated with the preimmunization antibody concentration. However, the geometric mean did not decrease significantly. Within 1 week of immunization, 85% of infants had an increase in antibody, significantly greater after the second dose than after the first. A high concentration of maternally derived antibody before immunization correlated negatively with antibody response. Thus, a transient decrease in antibody occurs in most adults and infants 2-3 days after immunization with PRP-OMP followed by a prompt increase by day 7.

Adult↗

A model of Staphylococcus aureus bacteremia, septic arthritis, and osteomyelitis in chickens.

We studied the occurrence, magnitude, and kinetics of bacteremia and the resultant osteomyelitis and septic arthritis in an avian model of Staphylococcus aureus infection. Thirty-day-old male broiler chicks were inoculated i.v. with 10(5), 10(6), or 10(7) cfu of strain Duntravis, a beta-hemolytic, coagulase-producing, capsular type 8 isolate from the synovial fluid of a 2-year-old black boy. Bacteremia occurred in 80%, 90%, and 100% of animals inoculated with 10(5), 10(6), or 10(7) cfu, respectively. The magnitude of bacteremia in surviving, bacteremic animals increased for 96 hours after inoculation and then decreased after a plateau phase. Osteomyelitis and septic arthritis occurred only in chicks that were continuously bacteremic. The occurrence of osteomyelitis was uniform among continuously bacteremic animals and developed 1 to 23 hours after inoculation. Chickens are susceptible to systemic infections with S. aureus. Bacteremia, osteomyelitis, and septic arthritis may be induced in healthy chickens without prior manipulations that depress their resistance.

Animals↗

Distribution and excretion of capsular antigen after immunization with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine.

The occurrence of Haemophilus influenzae type b capsular polysaccharide antigenemia and antigenuria following immunization was studied in 48 healthy 2-month-old infants. Each received a conjugate vaccine consisting of H. influenzae type b capsular polysaccharide covalently linked to Neisseria meningitidis serotype b outer membrane protein at 2 and 4 months of age. Infants were alternated at enrollment for collection of blood and urine after either the first or second dose. Specimens were obtained "early" (2-3 days) after immunization and "late" (7 days) after immunization and assayed for antigen. Antigen was detected in the serum of 3 (6%) of 48 infants, uniformly in the "early" specimen obtained after the first dose of vaccine. Antigenuria occurred in 37 (80%) of 46 infants; for greater than or equal to 7 days in 12 (26%). Antigenuria was frequent after administration of the vaccine but antigenemia was not. These data should be considered in the evaluation of an infant with suspected H. influenzae type b invasive disease.

Age Factors↗

Cost-benefit analysis of Haemophilus influenzae type b prevention: conjugate vaccination at eighteen months of age.

A cost-benefit analysis of Haemophilus influenzae type b disease preventive strategies was updated to consider evaluation of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) and H. influenzae type b oligosaccharide-mutant diphtheria toxin conjugate vaccine (HbOC) for children at 18 months of age. The analysis was done from the perspective of society as a whole. The economic costs of H. influenzae type b disease in the 1988 United States birth cohort would be $2.546 billion (1988 U.S. dollars) in the absence of preventive efforts. If 60% of all children could be vaccinated with PRP-D or HbOC at 18 months of age, this strategy would save $207.1 million ($88.22 savings/vaccinee; $43,605 cost/case prevented; 3.57/1 benefit-to-cost ratio) under base case model assumptions. Universal PRP-D or HbOC vaccination at 18 months of age would prevent 1845 cases of invasive H. influenzae type b disease. The break-even efficacy for universal PRP-D or HbOC vaccination at 18 months of age was 22.7%. We conclude that, under the model base case assumptions, universal PRP-D or HbOC vaccination at 18 months of age is sufficiently efficacious so that the costs of vaccination would be more than offset by decreased medical care costs for treating H. influenzae type b disease.

Bacterial Vaccines↗