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D M Granoff

Publications and source records attributed to D M Granoff.

At least 127 records · Page 7Linked to original sources
PubMed1983

Comparison of outer membrane protein subtypes of Haemophilus influenzae type b isolates from healthy children in the general population and from diseased patients.

Over a 12-month period we obtained throat cultures from 1,448 children less than 5 years of age attending well-child clinics and identified 24 carriers of Haemophilus influenzae type b (1.7%). The outer membrane protein subtypes of the strains from the carriers were compared to the subtypes of isolates from 50 patients with Haemophilus type b disease hospitalized in St. Louis, Mo., during the same period (1981 to 1982), and the latter were compared to the subtypes of isolates from 51 patients hospitalized between 1977 and 1980. There were no significant differences in the frequencies of the five most common subtypes (1L, 1H, 2L, 2H, and 3L), comparing isolates from the carriers to those from the patients. However, 5 of the 24 throat isolates had the unusual 13L subtype compared with only 1 of the 50 invasive isolates (P = 0.02). The lower frequency of 13L strains among the invasive isolates suggests that type b isolates with this subtype may be less pathogenic than type b isolates with other subtypes. Subtype 2L strains accounted for only 2% of recent cerebrospinal fluid or blood isolates, compared with 22% of those from 1977 to 1980 (P = 0.02). Subtype 1H and 3L strains together accounted for 73%, compared with 47% of the earlier ones (P = 0.02). Thus, temporal shifts may also occur in the subtype distribution of Haemophilus type b strains causing invasive disease in a community.

Bacterial Outer Membrane Proteins↗
PubMed1983

Purification and comparison of outer membrane protein P2 from Haemophilus influenzae type b isolates.

Haemophilus influenzae type b isolates have been subdivided based on differences in major outer membrane protein (OMP) profiles resolved on gradient and modified Laemmli sodium dodecyl sulfate-polyacrylamide gel electrophoresis systems. Although 21 subtypes have been observed, 86% of invasive isolates have one of five common subtypes and 71% of isolates have one of three subtypes. In isolates with two of the most common outer membrane subtypes, one major OMP has an apparent molecular weight of 37,000. In isolates with another common OMP subtype, a cross-reactive protein with an apparent molecular weight of 36,500 is observed. All three proteins have been designated P2. Protein P2 from these prototype isolates was solubilized with Zwittergent 3-14 and purified to homogeneity. Based on amino acid compositions, cyanogen bromide cleavage products, staphylococcal V8 protease, and chymotryptic peptide maps, the P2 protein from the three isolates has been highly conserved. Rabbit antibody prepared against P2 from one strain was cross-reactive with P2 isolated from the other two heterologous strains by Western blot. This antibody passively protected infant rats against type b Haemophilus infection caused by the homologous organism, but not against challenge by a strain with the heterologous 36,500 mol wt P2 protein. Thus, although the P2 protein from isolates with different OMP subtypes are closely related, the protection experiments suggest that determinants on the cell surface interacting with protective antibody may be strain or subtype specific.

Amino Acids↗
PubMed1982

Outer membrane protein subtypes and investigation of recurrent Haemophilus influenzae type b disease.

Ten previously healthy patients, ages 3 to 26 months, developed recurrent episodes of deep-tissue Haemophilus influenzae type b infections from 4 to 191 days (median = 28 days) after the last day of antibiotic therapy given for the first episode. None of the patients had a persistent focus of infection and eight were considered to have had adequate therapy for the initial episode. Bacteremia, without evidence of relapse at the site of the original infection, was documented in eight of the ten recurrent episodes. The ampicillin susceptibilities of the HITB isolates changed between episodes in two of the patients. Blood or CSF isolates from both episodes in seven patients were examined for biotypes and outer membrane protein subtypes. Concordance of both biotype and OMP subtype was present for all seven paired isolates, including the two pairs in which the HITB ampicillin sensitivities had changed. These data imply that some patients become reinfected with their original HITB isolates and that OMP and capsular antigens do not always elicit protective immunity, even after natural infection.

Ampicillin↗
PubMed1982

Human antibody responses to lipopolysaccharide after meningitis due to Haemophilus influenzae type b.

Levels of serum antibodies to lipopolysaccharide (LPS) were measured in acute- and convalescent-phase sera from 27 patients with meningitis due to Haemophilus influenzae type b using an enzyme-linked immunosorbent assay. The geometric mean titers of antibodies to LPS in acute-phase sera were similar to those of 24 control children and 22 healthy adults. In convalescent-phase sera there was a fourfold increase in the geometric mean titers of IgG and IgM antibodies to LPS. The antibody responses wee independent of age and of antibody response to the type b capsule. However, the responses were bimodal: children with high levels of IgG and IgM antibodies to LPS in acute-phase sera did not respond with further increases in serum antibodies to LPS after infection, whereas children with lower initial levels showed high responses. The presence of high levels of antibodies to LPS in the sera of half of the acutely ill children suggests that antibodies to some LPS determinants are not protective.

Adult↗
PubMed1982

Outer membrane protein and biotype analysis of pathogenic nontypable Haemophilus influenzae.

The techniques of biotype determination and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane protein preparations were applied to 35 epidemiologically unrelated isolates of pathogenic nontypable Haemophilus influenzae. Three of five isolates obtained from the blood of unrelated newborns with sepsis had concordant major outer membrane from the blood of unrelated older children or adults with bacteremia had concordant major outer membrane protein profiles, distinct from the common profile of neonatal strains, and were biotype II. The outer membrane protein profiles of the remaining 5 isolates from blood, 2 isolated from cerebrospinal fluid, and 23 isolated from middle ear aspirates of children with otitis media were unique, although each isolate had peptides with apparent molecular weights of 16,000 and 31,500. These results suggest that a subset of nontypable isolates associated with bacteremia has distinctive strain markers. Their pathogenicity may relate to a prediction for colonizing the female genital tract in the case of the common neonatal strain or an increased ability to evade host defenses.

Bacterial Proteins↗
PubMed1981

Rifampin prophylaxis for contacts of Haemophilus influenzae type b disease.

Rifampin prophylaxis (20 mg/kg once daily for four days) was used in close contacts of children with Haemophilus influenzae type b (HIB) disease. Two hours after a dose, the concentration of rifampin in serum and saliva exceeded the minimum bactericidal concentrations of organisms obtained from four of the carriers. In both a randomized prospective and an open study, nasopharyngeal carriage was eradicated in 37 (95%) of 39 contacts. No cases of serious H influenzae disease occurred in four to six months of follow-up. At the dose and treatment schedule used, rifampin was safe and effective for eradication of HIB carriage.

Adult↗
PubMed1981

Subtyping isolates of Haemophilus influenzae type b by outer-membrane protein profiles.

Outer-membrane proteins from isolates of Haemophilus influenzae type b were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sarcosinate-insoluble membrane preparations contained one peptide with a molecular weight of 16,000 and four major peptides with molecular weights of 25,000-40,000. A peptide with a molecular weight of 49,000 (50,000 in some strains) was observed after the samples were heated at 100 C. Fifty-one isolates obtained from patients hospitalized with invasive diseases, primarily meningitis, could be subclassified into nine categories based on reproducible and clearly resolvable differences in the outer-membrane protein profiles. Five categories accounted for 92% of the isolates. Complete concordance was observed in subtypes of strains obtained from epidemiologically related cases and contacts. Thus, comparison of the major outer-membrane proteins of H. influenzae type b is a useful technique for investigating the transmission of the organism and may provide a basis for further immunologic characterization of the outer-membrane proteins.

Animals↗
PubMed1981

Outer-membrane protein subtypes of Haemophilus influenzae type b and spread of disease in day-care centers.

Isolates of Haemophilus influenzae type b with a distinctive outer-membrane protein subtype, designated 1H, were responsible for 11 of 13 cases of invasive infection in children attending six day-care centers with secondary cases of disease, in comparison to three of 14 cases in children attending 10 centers with single cases and two centers with unrelated cases. The other 11 cases were caused by type b isolates of six different subtypes. The secondary attack rate in contacts younger than four years of age exposed to disease due to isolates of the 1H subtype was 16 per 1,000, compared with 1.6 per 1,000 after exposure to disease caused by subtypes other than 1H (P less than 0.008). Carriage rates were increased in day-care-center contacts exposed to patients with disease, and most of the carriers were colonized by isolates with subtypes homologous to those responsible for the respective index cases. Both 1H and non-1H strains were capable of colonizing contacts, but 1H strains may be more pathogenic than other subtypes.

Bacterial Proteins↗
PubMed1980

Haemophilus influenzae infections in Fresno County, California: a prospective study of the effects of age, race, and contact with a case on incidence of disease.

A prospective, population-based study of the incidence of infections with Haemophilus influenzae in Fresno County, California, was conducted. The average annual incidence or meningitis was 5.18 cases per 100,000 population, and of other invasive infections, 3.48 cases per 100,000. Incidence rates were highest in infants, but 13% of infections and five of seven deaths were in adults, primarily in elderly individuals with compromised defenses. Black children four years of age and younger were more susceptible to meningitis due to H. influenzae than were white children (P less than 0.001). In contrast, the increased incidence of haemophilus disease in Hispanic children was primarily a result of invasive infections other than meningitis (P less than 0.03). The secondary attack rate in household contacts less than two years of age was one in 24 during the first 30 days, one in 23 between 31 and 60 days, and 0.25 in 22 per month between three and six months. Age and racial factors may affect susceptibility to different forms of invasive disease due to H. influenzae, and young contacts of a patient are at increased risk of developing illness.

Adolescent↗
PubMed1980

Haemophilus influenzae type b in a day care center: relationship of nasopharyngeal carriage to development of anticapsular antibody.

We measured anticapsular antibody to Haemophilus influenzae type b by radioimmunoassay in sera from 55 children attending a day care center in which two cases of H influenzae type b disease had occurred. The children ranged in age from 2 months to 36 months. Serum antibody levels in children attending the day care center were significantly higher than in age-matched controls (P less than .001), but in two different surveys one month apart 38% and 43% of the contacts had levels less than 100 ng/ml. Day care center children who were carriers of H influenzae type b had higher geometric mean antibody levels than noncarriers (478 ng/ml compared to 92 ng/ml, P less than .004). Nevertheless, six of 21 children (29%) with repeatedly positive cultures during four weeks of observation had concentrations of serum antibody less than 100 ng/ml when measured both by binding the 125I-derivative of the capsular antigen (polyribosyl-ribitol phosphate), or binding of 3H-polyribosyl-ribitol phosphate. These data may explain observations of H influenzae type b disease in contacts of cases more than 30 days after hospitalization of the index patient.

Antibodies, Bacterial↗
PubMed1980

Comparison of rifampin and ampicillin in day care center contacts of Haemophilus influenzae type b disease.

A prospective, randomized, crossover trial was conducted comparing therapy with rifampin to therapy with ampicillin in eradicating Haemophilus influenzae type b carriage. Twenty-eight carriers were identified in a day care center following exposure to a patient with H influenzae type b meningitis; 26 children were randomly assigned to treatment with either ampicillin (100 mg/kg for five days) or rifampin (20 mg/kg for four days). Cultures were repeated two and four days after discontinuing therapy. In the initial trial, 6/17 children (35%) remained culture positive after treatment with ampicillin compared to 0/9 children treated with rifampin (P = .106). The six children who were ampicillin treatment failures had H influenzae type b isolates sensitive to that drug. These children were subsequently treated with rifampin and their cultures became negative. (For both trials, P = .027). Repeat cultures 30 days after therapy in 20 treated children revealed one culture positive for H influenzae type b. No further cases developed in the day care center (four months of follow-up). These data suggest that rifampin may be more effective than ampicillin in chemoprophylaxis of contacts of H influenzae type b disease.

Ampicillin↗