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Biomedical subjects

H R Shinefield

Publications and source records attributed to H R Shinefield.

At least 19 recordsLinked to original sources

Safety, immunogenicity, and efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b vaccine in a United States population: possible implications for optimal use.

Between February 1988 and June 1990, the safety, immunogenicity, and efficacy of Haemophilus influenzae type b (Hib) oligosaccharide conjugate (HbOC) vaccine was evaluated in a prelicensure trial of 61,080 children. HbOC was found to be safe and immunogenic in infancy. Extended follow-up revealed that as of 31 December 1990, 30 cases of invasive Hib disease had occurred in 74,699 children; 26 were in unvaccinated children and 4 in children who had received only one dose. No disease occurred in children who had received two or three doses. By 30 September 1991, another case had occurred in an unvaccinated child. Comparison of these efficacy data with those of Hib capsular polysaccharide-outer membrane protein conjugate vaccine (PRP-OMP) reveals that both were effective in preventing disease in the first year of life. However, the small cohort in the PRP-OMP study did not allow demonstration of duration of protection beyond 1 year. Ongoing surveillance in larger populations is necessary to allow comparison of the duration of immunity provided by these vaccines.

Antibodies, Bacterial

Antimicrobial activity of sphingosines.

The antimicrobial activity of stratum corneum lipids was examined by screening in vitro various representative phospholipids and sphingolipids. Of mixed galacto-cerebrosides; phosphatidic acid; phosphatidic acid-monomethylester-dioleoyl; phosphatidylethanolamine; phosphatidylethanolamine-beta-oleoyl-gamma-palmitoyl; phosphatidylcholine; D-sphingosine; D,L-sphinganine; 4-D-hydroxysphinganine; oleoyl-sphingosine; N,N-dimethylsphingosine; and stearylamine, only the sphingosines and, to a lesser extent, stearylamine were clearly and profoundly effective against Staphylococcus aureus (4-log reduction at 6.25 micrograms/ml [20 microM]; 2-log reduction at 0.78 mu/ml [2.5 microM]). The sphingosines were similarly active against Streptococcus pyogenes, Micrococcus luteus, Propionibacterium acnes, Brevibacterium epidermidis, and Candida albicans, moderately active against Pseudomonas aeruginosa, and ineffective against Escherichia coli and Serratia marcescens. Both erythro- and threo-isomers were effective. Optimal inhibition was at 60 min incubation at 37 degrees C and at pH 6.5. Antimicrobial activity, which was Ca++ dependent, was confirmed in vivo by topical application and microbial challenge. Because free sphingosines are available in the stratum corneum and other epidermal layers, these lipids may contribute to the cutaneous antimicrobial barrier.

Bacteria

Inhibition of microbial adherence by sphinganine.

Sphingosines (precursors and degeneration products of complex sphingolipids) are mediators in membrane second-messenger cascades and in a wide variety of functions in eukaryotic cells. Sphingosines are also lethal for gram-positive microorganisms. In addition to its direct effect, sphinganine is here reported to affect the adherence of Streptococcus mitis to buccal epithelial cells and of Staphylococcus aureus to nasal mucosal cells after incubation for 90 min at 37 degrees C. When the bacteria were pretreated with 8.1, 16.2, 32.5, or (for Strep. mitis) 65 microM sphinganine for 60 min at 37 degrees C, adherence counts were reduced for Staph. aureus by 27, 37, and 60% and for Strep. mitis by 19, 44, 54, and 73%, respectively (p < 0.001). In contrast, pretreatment of buccal cells with 81.2 microM lipid increased adherence by 14% (p < 0.01), but no change occurred at either 16.2 or 325 microM lipid. These results further demonstrate the double-edged ability of sphingosines to regulate cellular activities and their potential as multifunctional therapeutic agents for infectious diseases.

Bacterial Adhesion

Immunization with oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine on a large health maintenance organization population: extended follow-up and impact on Haemophilus influenzae disease epidemiology. The Kaiser Permanente Pediatric Vaccine Study Group.

Between February, 1988, and June, 1990, the safety, immunogenicity and efficacy of the HbOC (oligosaccharide conjugate Haemophilus influenza type b) vaccine was evaluated in a prelicensure trial performed in a study population of 61,080 children within the Northern California Kaiser Permanente Medical Care Program. In this evaluation the HbOC vaccine was found to be safe, immunogenic and efficacious in infancy. Since licensure an estimated 162,000 additional doses of HbOC vaccine have been given to 75,000 additional children. In addition to reporting on extended follow-up of this population, this publication reports on the impact of immunizing a high proportion of the Northern California Kaiser Permanente Medical Care Program population in infancy and early childhood on the epidemiology of invasive disease caused by H. influenzae type b (Hib) and invasive disease caused by non-type b H. influenzae. As of January 31, 1992, six cases of Hib invasive disease have been identified in vaccinated children. Of these five occurred in children who had received only one dose of vaccine in infancy. One case of Hib meningitis occurred in a 3 1/2-year-old child who had received doses of HbOC at 2, 4 and 6 months of age but no further doses of any Hib vaccines. During 1991 a total of three cases of invasive disease caused by Hib were observed in children younger than 18 months of age within the Northern California Kaiser Permanente Medical Care Program. This represents a 94% reduction in disease incidence in this age group from that observed in the years 1984 to 1987.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins

Safety and immunogenicity of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in infancy. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group.

The safety and immunogenicity of the HbOC conjugate vaccine have been evaluated in a study population of 61,080 children in the Kaiser Permanente Medical Care Program of Northern California. Half of the population served as controls. The vaccine was given as part of a three-dose regimen in the first year of life with the first dose given between 6 weeks and 6 months of age, a minimum interval of 1 month between doses and with the third dose given by 1 year of age. The vaccine was highly immunogenic with 97% of infants developing 1 microgram/ml or more of anti-polyribosyl phosphate antibody as measured by Farr assay 1 month after completion of the three-dose series and with 71% maintaining this concentration until a booster dose was given at approximately 18 months of age. There were three cases of Haemophilus influenzae type b disease after the first dose of vaccine and two of these children died. However, there was no statistically significant difference between either the incidence of H. influenzae type b disease or the mortality rate in infants after one dose of HbOC vaccine when compared with H. influenzae type b disease incidence and mortality in unvaccinated children of the same age. The rate of sudden infant death syndrome following HbOC vaccine was lower than that observed within the Kaiser Permanente Medical Care Program as a whole or in the three counties in which sudden infant death syndrome surveillance was tabulated. Immediate local and systemic reactions were evaluated by telephone interviews of 6887 infants within 72 hours of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial

Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61,080 children. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group.

The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61,080 infants in the Northern California Kaiser Permanente Medical Care Program. Between February, 1988, and June, 1990, the HbOC vaccine was given as part of a three-dose series at 2, 4, and 6 months of age to 20,800 infants. The study population included children with a well-care visit at a study center during the first 6 months of life. There were 25 cases of Haemophilus influenzae type b disease in the study population: 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine. The efficacy of the full three-dose series was evaluated by several methods: a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age; a stratified exact analysis adjusted for age and seasonality; and a case-control analysis which further adjusted for known risk factors. The efficacy of three doses of vaccine was 100% with the lower bound of the 95% confidence interval for the three analyses at 68, 71, and 64%, respectively. There were no cases of disease resulting from two doses of HbOC vaccine yielding an estimate of 100% efficacy (95% confidence interval, 47 to 100) for two doses of HbOC vaccine. However, for children who had received only one dose of HbOC vaccine, vaccine efficacy was estimated to be 26% and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins

Apparent decreased risk of invasive bacterial disease after heterologous childhood immunization.

To investigate the possibility that there might be an increased risk of heterologous invasive bacterial disease after routine childhood immunization with measles, mumps, and rubella vaccine live; diphtheria and tetanus toxoids and pertussis vaccine; and oral poliovirus vaccine live, a case-control study was conducted within the Kaiser Permanente Northern California pediatric population. Contrary to the premise, an apparent protective effect against invasive bacterial disease was detected after all childhood vaccinations. However, when adjustment was made for frequency of well-care visits and day-care attendance, no significant relationship was seen between receipt of routine childhood immunizations and risk of invasive heterologous bacterial disease for any individual vaccine, although a statistically significant protective effect was detected within 1 or 3 months after the receipt of any vaccine. Since a decreased risk of invasive bacterial disease was also noted to be related to the receipt of routine well-child pediatric care, other preventive health care measures may be responsible for the apparent immunization protective effect.

Bacterial Infections

Antimicrobial activity of stratum corneum lipids from normal and essential fatty acid-deficient mice.

Among the cutaneous effects of an essential fatty acid deficient (EFAD) diet are hyperdesquamation, increased transepidermal water loss (TEWL), and altered lipid profiles, characteristics also common to inflammatory dermatoses. Because fatty acids are antimicrobial, we examined the indigenous skin flora of normal and EFAD hairless mice, and compared the antimicrobial efficacy of lipids extracted from their stratum corneum. EFAD mice supported 100-fold more bacteria than normal mice, and were the only group from which Staphylococcus aureus were routinely isolated. Despite this greater carriage, in vitro experiments demonstrated that EFAD lipids are more lethal than normal lipids against Streptococcus pyogenes, S. aureus, S. epidermidis, Micrococcus sp., and a coryneform. Skin fungi were equally susceptible to both extracts. After thin layer chromatography, the most active fractions were found to be glycosphingolipids and phospholipids. EFAD extracts had 35% more free fatty acids and 75% more glycosphingolipids; normal extracts had more triglycerides and phospholipids. S. aureus strain 502A survived equally well on EFAD as on normal mice. Normal lipids applied on EFAD mice had no additional effect, but EFAD lipids on normal mice brought about a 35% reduction of the inoculated bacteria. If the mice were pretreated with alcohol, carriage of strain 502A was reduced by 71%. If instead the mice were previously washed with acetone to increase TEWL, a 97% reduction of the staphylococcus occurred. The application of normal flora to such acetone-washed mice decreased the efficacy to 76%. EFAD and normal lipids on human subjects were equally ineffective in eliminating strain 502A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Efficacy of Haemophilus influenzae type b capsular polysaccharide vaccine.

The efficacy of the Haemophilus influenzae type b (Hib) polyribose phosphate vaccine was evaluated in a population of 120,000 children from 23 through 71 months of age in the Kaiser Permanente Medical Care Program (KPMCP) in Northern California over the 2-year period from June 1, 1985, through May 31, 1987. Approximately 37% of the population were vaccinated by the end of the first year and 60% were vaccinated by the end of the second year. There were 35 cases of Hib disease, 4 of whom were vaccine failures. Cases of Hib disease were identified by multiple modality case ascertainment, consisting of: (1) active surveillance in KPMCP microbiology laboratories; (2) active surveillance on KPMCP pediatric wards by a study physician; (3) retrospective review of computer-stored hospital discharge diagnoses; and (4) a review of all hospitalizations outside the health plan. The medical records of cases, matched controls and a random sample of the population were reviewed to obtain information on vaccination and related variables. Efficacy was evaluated using two complementary methods. In a retrospective surveillance approach, efficacy was estimated to be 68% (95% confidence limits of 4, 89%). In a matched case-control analysis, efficacy was estimated to be 69% (95% confidence limits of -13, 91%). Adjustment for day care attendance and parental occupation slightly reduced the efficacy estimate. Other possible confounders including race, parental education and number of siblings were considered. Four cases of Hib disease were observed within 1 week following receipt of vaccine and before the time when immunity could have developed. There are several plausible explanations for the occurrence of these early cases including the possibility of chance alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Capsules

Microbial adherence to vulvar epithelial cells.

Under uniform experimental conditions, different degrees of selective attachment of Staphylococcus aureus and Candida albicans to epithelial cells of the labium majus, the labium minus, and the vagina were compared and contrasted with those found in studies with cells of the buccal and nasal mucosa and forearm skin by a novel analysis of adherence density. For both micro-organisms, the larger, rougher cells of the labium majus gave the highest adherence scores matched only by the interaction of S. aureus with fully keratinised nasal epithelial cells. Increasing acidity to pH 3.5 enhanced microbial adherence to vaginal cells. Menstruation also influenced attachment; highest densities were reached between the third and fourth weeks of the cycle. Autogenous ribitol teichoic acid was found to block the attachment of S. aureus to labium majus and labium minus cells by 76% and 81% respectively, and to vaginal cells by 66%. Adherence is considered to be an important attribute of vulvar ecology and may be a determinant of infectious disease.

Adhesiveness

b-CAPSA I Haemophilus influenzae, type b, capsular polysaccharide vaccine safety.

The b-CAPSA I capsular polysaccharide vaccine for Haemophilus influenzae type b was given to 87,541 children 2 through 5 years of age in the Kaiser Permanente Medical Care Program, and the children were then followed using a multiple modality surveillance. Phase 1 consisted of 24-hour recall of immediate side effects which were recorded on questionnaires given to families of 13,500 children. Local side effects were found to be uncommon: 2.3% had a temperature of greater than or equal to 38.3 degrees C (greater than or equal to 101 degrees F); 4.8% had local erythema, 2.9% local swelling, and 12.6% local tenderness; two children had wheezing shortly after immunization. In Phase 2, 30 days after immunization, questionnaires were mailed to parents of all 87,541 children, who were asked to respond to questions about illnesses and health care. Phase 3 consisted of active surveillance of patient health care use by physicians and nurses during the 30 days after immunization. During the 30-day reporting periods, there were 40 hospitalizations, including one for wheezing and one for febrile seizure. Of the 40 hospitalizations, only the one for wheezing was believed by the admitting physician to be probably associated with vaccine administration. Three children had seizures within 30 days of immunization. None of the seizures was believed by the reporting physician to be associated with immunization. Adverse effects of the vaccine were mild, limited to local reactions and occasional temperature elevation; bronchospasm after immunization occurred rarely.

Bacterial Capsules

The Staphylococcus aureus receptor for fibronectin.

The Staphylococcus aureus binding site for human fibronectin was determined by unique biologic assays based upon the specific adherence of the bacterium to nasal epithelial cells. Fibronectin treatment of S. aureus caused a reduction in adherence tallies on high granular and fully keratinized cells compared to controls (p less than 0.05; p less than 0.001). Spinous and low granular cells showed no significant differences. The cell wall materials N-acetyl-D-glucosamine, N-acetyl muramic acid, and protein A were unable to inhibit the coupling of fibronectin to S. aureus. Only ribitol teichoic acid had this property. Furthermore, fibronectin could neutralize the adherence-blocking ability of teichoic acid, which affects keratinized cells. Thus, teichoic acid seems to be a receptor for fibronectin.

Binding Sites

Competitive adherence as a mechanism of bacterial interference.

To determine whether competition among bacteria for specific attachment sites on host cells can explain bacterial interference, Staphylococcus aureus strain 502A was tested in turn against two different nasal coryneforms, a strain of Pseudomonas aeruginosa, and a virulent strain of S. aureus, all in the presence of nasal mucosal cells. Particularly examined was the influence of sequence in which bacteria were presented to the nasal cells in comparison with initial mixtures and individual suspensions. Results paralleled those observed in clinical prophylaxis: the bacterium first to adhere to the epithelial cells was able, under uniform conditions, to interfere with the colonization of subsequently added bacteria. Secondary adherence was not eliminated but substantially reduced, and was probably related to steric blockage by the initial colonizer and its particular ability to dissociate from the host cell.

Adhesiveness

Indirect hemagglutination inhibition: a direct method for detecting cytomegalovirus antigen.

We have developed a simple and sensitive technique for detecting CMV antigen in tissue culture specimens. The IHI assay is a modification of the IHA, which is capable of reliably detecting 10(3) median TCID50 of virus. With the IHI assay, antigen is detected by its capacity to inhibit the reactivity of CMV antisera of known titer in an IHA assay. The test is specific, uses readily available reagents, and is easy to perform. The IHI assay may serve as a tool for screening tissue culture specimens for CMV.

Antigens, Viral

Importance of the keratinized epithelial cell in bacterial adherence.

The effect of cellular pathology and keratinization of skin and nasal cells upon binding of Staphylococcus aureus were examined. Adherence with epithelial cells obtained from either the skin or nasal mucosa of patients with atopic dermatitis was greater than that observed with normal cells (p less than 0.001); the difference in adherence between psoriatic and normal cells was not statistically significant. Tested nasal cells were microscopically differentiated into 4 general types based on stage or layer of keratinization: spinous, low granular, high granular, and keratin. The degree of adherence was related to the progress of keratinization. Data indicated the existence of 2 types of receptors for S. aureus on nasal cells: One, present upon both granular and fully keratinized cells, is not blocked by teichoic acid and appears responsible for the higher bacterial counts on atopic cells; the second is found on keratinized cells only and is susceptible to teichoic acid.

Adhesiveness

Hemoglobin concentration in white, black, and Oriental children: is there a need for separate criteria in screening for anemia?

The concentration of hemoglobin in blacks was found to be 0.5 to 1.0 g/dl lower than that of income-matched whites in several large surveys. This difference could be a racial characteristic of blacks, or it might be due to a higher frequency of genetic traits such as thalassemia minor and hemoglobinopathies, or to environmental factors such as iron deficiency. To help in making this distinction, we analyzed the data from multiphasic examinations (1973 to 1975) on 1718 white, 741 black, and 315 Oriental healthy, nonindigent children between 5 and 14 years of age. In the entire population, the median hemoglobin concentration averaged 0.5 g/dl lower in blacks than in whites of both sexes (t test, P less than 0.001). The differences still averaged 0.5 g/dl (P less than 0.001) after exclusion of all those with abnormal hemoglobin by electrophoresis (Hgb S and C) and those whose mean corpuscular volume was more than 5% below the normal mean for age (to exclude iron deficiency or thalassemia minor). The data strengthen the impression that blacks normally have a concentration of hemoglobin averaging about 0.5 g/dl less than in whites. If this is the case, about 10% of normal blacks will be mistakenly designated anemic, if the same norms are applied.

Adolescent

Microbial flora of atopic dermatitis.

The microbial flora of dermatitic skin, uninvolved skin, and the anterior nares of subjects with atopic eczema were investigated. The carriage rate of Staphylococcus aureus was 79% for the anterior nares, 76% for the uninvolved skin (normal skin), and 93% for lesions. The counts of S aureus were 7.5 X 10(4)/sq cm in lesions and 7.1 X 10(3)/sq cm on adjacent normal skin. Staphylococcus aureus was the predominant organism in the lesions and constituted 91% of the total aerobic bacterial flora. The coagulase-negative staphylococci were the second predominant organisms (9%). On normal skin, coagulase-negative staphylococci were the predominant organisms, constituting 63% of the total flora, followed by S aureus (30% of the bacterial flora). The micrococci counts were lower in the lesions (1.6 X 10(2)/sq cm) and higher on normal skin (9.5 X 10(2)/sq cm). Lipophilic diphtheroids were fewer on normal skin (6.7 X 10/sq cm), and there were none in the lesions. Fifty-eight percent of the strains belonged to group 3, and 38% were nontypeable. Staphylococcus aureus strains belonging to phage groups 2 and 4 were not detected.

Adolescent