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Biomedical subjects

R S Daum

Publications and source records attributed to R S Daum.

At least 73 records · Page 4Linked to original sources

Disease caused by Haemophilus influenzae type b in the immediate period after homologous immunization: immunologic investigation.

Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States. These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b, alone or covalently bound to one of several carrier proteins. Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D) and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC). Two others, a polysaccharide-Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) and a polysaccharide-tetanus toxoid conjugate (PRP-T), are currently in clinical trials. One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources. In a case-control study of the efficacy of PRP vaccine, Black et al found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval [CI], 2.1 to 19.2) than the background rate in unvaccinated children. In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9), and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Decline in serum antibody to the capsule of Haemophilus influenzae type b in the immediate postimmunization period.

STUDY OBJECTIVE: To determine what change, if any, occurs in the serum anticapsular antibody concentration immediately after immunization with either Haemophilus influenzae type b capsular polysaccharide vaccine (PRP) or a vaccine consisting of the capsular polysaccharide conjugated to diphtheria toxoid (PRP-D). SETTING AND PATIENTS: Children: a convenience sample of 32 healthy 2-year-old children from diverse locales. Adults: a convenience sample of 16 healthy adults chosen from employees at the Washington University and Tulane University schools of medicine. INTERVENTIONS: PRP or PRP-D vaccine administered to the adults and serum obtained daily for 5 days. PRP vaccine was administered to the children, and serum was sampled 2 or 3 days or 4 or 5 days after immunization, or both. MEASUREMENTS AND MAIN RESULTS: Decline in serum antibody in all seven (100%) adult recipients of PRP. The nadir occurred on days 1 to 3, and the decrease average 26.0% of the preimmunization concentration. Eight (89%) of nine PRP-D recipients had a similar decline that averaged 25.9%. Of 29 children, 20 (69%) had a decline that averaged 14.7%. The magnitude of anticapsular antibody present before immunization was correlated with the magnitude of the observed decrease. CONCLUSIONS: A decrease in serum anticapsular antibody occurs in most children and adults immunized with PRP (adults and children) or PRP-D (adults). Such a decrease might transiently increase the risk of invasive disease if it occurred during a period of asymptomatic colonization with H. influenzae type b.

Adult↗

Intrarenal abscess caused by Klebsiella pneumoniae in a neonate: modern management and diagnosis.

We recently cared for a 12-day-old infant who was hospitalized for renal abscess caused by Klebsiella pneumoniae, an organism not identified as etiologic in the three newborns described to date with this disorder. The advent of cross-sectional diagnostic imaging techniques, specifically ultrasonography and computed tomography (CT), has changed the management of renal abscess in children and neonates. Ultrasonography is the diagnostic procedure of choice, but CT is another reliable imaging modality, particularly if there is spread of the abscess outside the kidney. Whether surgery is necessary for a resolution of renal abscess remains controversial. However, percutaneous aspiration under diet ultrasonographic or CT guidance has replaced routine exploration and deroofing of the abscess and therefore made the management of renal abscess achievable by simpler, less invasive techniques.

Abscess↗

Postvaccination susceptibility to invasive Haemophilus influenzae type b disease in infant rats.

To evaluate the possibility that immunization with a capsular polysaccharide vaccine decreases immunity in the immediate postvaccination period and renders an animal susceptible to invasive Haemophilus influenzae type b disease, we passively immunized infant rat pups with an immune globulin preparation, vaccinated them with an H. Influenzae type b capsular polysaccharide vaccine at a wide range of doses, and challenged them with H. influenzae type b given intraperitoneally. Bacteremia occurred in 89% of protected, vaccinated pups compared with 17% of protected, unvaccinated pups (p = 0.0001). In protected, vaccinated pups the rate of bacteremia resembled that in unprotected, unvaccinated control pups and did not vary with the dose of vaccine administered. The magnitude of bacteremia and the incidence of meningitis in protected, vaccinated pups exceeded that occurring in the protected, unvaccinated control animals, but these effects diminished with the dose of vaccine. Diminution of anticapsular antibody occurred in association with the largest doses of vaccine. We conclude (1) that the administration of H. influenzae type b capsular polysaccharide vaccine in infant rats is associated with a diminution of passively acquired anticapsular antibody immediately after vaccination and (2) that experimental challenge with H. influenzae type b at this time produces disease resembling that in animals not passively given protection.

Animals↗

Epidemiology of rob beta-lactamase among ampicillin-resistant Haemophilus influenzae isolates in the United States.

We surveyed 161 clinical isolates of ampicillin-resistant, beta-lactamase-producing isolates of Haemophilus influenzae obtained between 1975 and 1985 to determine whether they produced TEM-1 or Rob beta-lactamase. Plasmid DNA was obtained from a Rob-producing isolate, F990, and a plasmid (pBR322) known to encode TEM-1. Both plasmids were labeled with 32P and hybridized to whole cell DNA obtained from the clinical isolates. All 161 isolates hybridized with one of the plasmid probes and could be classified as TEM-1- or Rob-producing isolates. Analysis of the distinctive pH profiles of the two beta-lactamases was used to confirm the findings of the DNA hybridization assay. Overall, 13 (8%) isolates obtained from patients in California, North Carolina, Tennessee, Missouri, Louisiana, and Mississippi produced the Rob beta-lactamase. The remaining isolates elaborated the TEM-1 enzyme. We conclude that ampicillin resistance in H. influenzae may be mediated by the production of Rob beta-lactamase and that the occurrence of this enzyme is not limited to the two isolates described to date.

Ampicillin Resistance↗

Gentamicin penetration into cerebrospinal fluid in experimental Haemophilus influenzae meningitis.

We studied the effect of meningitis and the method of parenteral gentamicin administration (intramuscular injection, a 30-min intravenous infusion, or intravenous bolus administration) on achievable concentrations of drug in cerebrospinal fluid (CSF). In normal animals, only intravenous bolus administration of 2 to 8 mg/kg produced a gentamicin concentration of greater than 0.1 microgram/ml in CSF in some animals. All CSF samples contained less than the limit of detection (0.1 microgram/ml) after the intramuscular administration of 6 mg/kg. In animals with meningitis, gentamicin penetration into cisternal CSF was increased significantly after a bolus administration of 6 mg/kg (mean, 0.197 +/- 0.063 microgram/ml in normal animals versus 1.68 +/- 0.38 micrograms/ml in animals with meningitis; P less than 0.01). In meningitic animals that received 6 mg/kg as an intravenous bolus, lumbar CSF had the highest maximum concentration (4.25 +/- 1.08 micrograms/ml), in comparison with ventricular CSF (3.10 +/- 0.66 micrograms/ml). The gentamicin concentration in cisternal CSF decreased more slowly than it did in serum (elimination half-life, 238.70 +/- 64.56 min in cisternal CSF versus 82.73 +/- 2.91 min in serum), yielding a relative increase in the percentage of penetration. We conclude that maximum penetration by gentamicin into CSF occurs after intravenous bolus administration and that the maximum concentration occurs in lumbar CSF.

Animals↗

Evaluation of a commercially available latex agglutination test for rapid diagnosis of group B streptococcal infection.

We studied the clinical value of Wellcogen, a latex particle agglutination test designed to diagnose rapidly Group B streptococcal infections in 620 infants. The sensitivity and specificity were 18 of 20 (90%) and 18 of 22 (81%), respectively. False negatives were documented in 2 patients and false positive tests occurred in 4. Also 10 of 620 (1.6%) infants had detectable antigen in the absence of proved infection. In addition, in 4 other infants with Group B streptococcal bacteremia, antigenemia was absent in serum obtained on the day of hospitalization but antigen was detected in specimens obtained subsequently. We also assayed the sera of 102 randomly chosen hospitalized adults; 4 (4%) contained "antigen" but none had Group B streptococcal infection. None of 50 urines obtained from other randomly chosen hospitalized adults contained "antigen." In patients with Group B streptococcal meningitis cerebrospinal fluid and unconcentrated urine uniformly contained antigen but in bacteremia without focality, assay of blood and urine were both necessary to diagnose correctly all 7 patients with the Wellcogen test. We conclude that despite acceptable sensitivity and specificity, the interpretation of the Wellcogen test must be performed with caution and knowledge of its limitations.

Adult↗

Cost-benefit analysis of two strategies for prevention of Haemophilus influenzae type b infection.

A cost-benefit analysis for Haemophilus influenzae type b disease prevention was developed to examine two officially recommended preventive strategies: H influenzae type b capsular polysaccharide immunization and rifampin prophylaxis of exposed contacts. The social costs of H influenzae type b disease in the 1984 US birth cohort will be $1.937 billion when base case assumptions are made. If it is assumed that 60% of all children could be vaccinated at 24 months of age, universal vaccination has the highest economic benefits of any single preventive strategy considered (net savings $64.8 million). Rifampin prophylaxis of appropriate household contacts has the highest benefit to cost ratio (59:1), but because rifampin prevents only secondary disease, only half as many cases can be prevented with rifampin prophylaxis of appropriate household contacts (501 cases prevented, $1,994 per case prevented) as with universal vaccination at 24 months (985 cases prevented, $63,484 per case prevented). Single-dose vaccination of day-care attendees at 18 months of age is the most expensive preventive strategy considered ($148,445 per case prevented, 306 cases prevented). Rifampin prophylaxis of appropriate day-care contacts prevents the fewest H influenzae type b cases ($46,041 per case prevented, 72 cases prevented.

Adolescent↗

Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine.

We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine. The geometric mean concentration of antibody to type b polysaccharide in convalescent-phase serum from 31 of the vaccinated patients who had hemophilus disease was significantly lower than that in serum from 25 patients of similar age with the disease who had never been vaccinated (0.59 vs. 3.46 micrograms per milliliter, P less than 0.001). However, only 3 of 46 patients in whom the vaccine failed and who were tested for hypogammaglobulinemia had this finding, and none of 33 children tested for IgG2 had low serum concentrations of this immunoglobulin subclass, which is thought to be important in the immune response to polysaccharide antigens. In addition, all but 1 of the 46 patients in whom the vaccine failed and who were tested for IgG antibody to tetanus toxoid protein, a thymic-dependent antigen, had normal values, and 19 of 20 tested for hemolytic complement activity had normal levels. In white children, the presence of the Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was associated with a sevenfold increase in the relative risk of vaccine failure (P less than 0.003). We conclude that vaccine failure may be related in part to genetic factors, and that most vaccinated children in whom Hemophilus influenzae disease develops have deficient antibody responses to the type b polysaccharide despite normal serum concentrations of immunoglobulin and normal antibody responses to tetanus toxoid.

Antibodies, Bacterial↗

Pathogenicity of a rifampin-resistant cerebrospinal fluid isolate of Haemophilus influenzae type b.

Two children in a day care facility developed Haemophilus influenzae type b meningitis. The second child was enrolled in the facility after rifampin had been administered to the other attendees. The isolate from the first child was susceptible to rifampin, but the isolate from the second was resistant. Both isolates had identical outer membrane protein PAGE profiles. To investigate the virulence of these isolates, we inoculated infant rats intranasally with either the rifampin-resistant or rifampin-susceptible CSF isolate. The rates of nasal colonization (14 of 20 and eight of eight animals inoculated with the rifampin-resistant and rifampin-susceptible isolates, respectively) did not differ significantly. However, bacteremia occurred less frequently in pups inoculated with the rifampin-resistant strain than in animals inoculated with the susceptible strain (four of 20 vs eight of eight, P less than 0.0001). Nasal washings, blood, and CSF obtained from animals inoculated with the rifampin-resistant isolate were divided and plated on media containing rifampin (1 microgram/ml) or without rifampin. Except for those from one animal, organisms isolated from blood and CSF grew only on medium lacking rifampin, whereas H. influenzae type b growing from nasal washings was frequently found on both media. We conclude that mutation of H. influenzae to rifampin resistance is a hazard of rifampin chemoprophylaxis. Rifampin-resistant isolates have the potential to cause disease in patients and experimental animals, although they may be relatively less pathogenic than the parent, susceptible organism.

Animals↗

Toxic epidermal necrolysis in a 6-week-old infant.

Toxic epidermal necrolysis was documented in a 6-week-old infant with Klebsiella pneumoniae sepsis who received many medications. We inoculated infant mice with the K. pneumoniae isolate but were unable to produce histologic changes resembling those seen in our patient. This condition should be included in the differential diagnosis of severe drug reactions in very young infants with clinical scalded-skin syndromes.

Animals↗

Effect of rifampin chemoprophylaxis on carriage eradication and new acquisition of Haemophilus influenzae type b in contacts.

We conducted a multicenter trial designed to assess the efficacy of three different drug regimens on eradication of Haemophilus influenzae type b (HIB) from the nasopharynx of household contacts of patients with invasive type b Haemophilus disease. The drug regimens studied were rifampin, 20 mg/kg, once daily for four days; rifampin, 10 mg/kg, twice a day for four days; and placebo, once daily for four days. Shortly after admission of the index patient to the hospital, 26% of 492 household contacts were found to be colonized with HIB. Both rifampin regimens eradicated carriage significantly better than placebo at 10 and 30 days (P = .001). However, among contacts whose cultures were initially negative, new acquisition of the organism occurred infrequently in this 30-day follow-up period regardless of the drug or placebo regimen prescribed. We also measured the concentration of anticapsular antibody in sera obtained from contacts younger than 6 years of age. Samples were obtained soon after admission of the index patient to the hospital and 30 days later. Several carriers younger than 2 years of age had low concentrations of antibody in both specimens. In contrast, nearly all carriers 2 to 5 years of age had high concentrations of antibody even in the first sample. Children who were not carriers usually had low antibody concentrations which did not increase during the period of observation. Our results suggest that most intrafamilial spread of HIB occurs prior to hospitalization of the index patient and stimulates immunity in contacts older than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗