PubMed Health⌕ Search

Biomedical subjects

S A Halperin

Publications and source records attributed to S A Halperin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Acellular pertussis vaccine as a booster dose for seventeen- to nineteen-month-old children immunized with either whole cell or acellular pertussis vaccine at two, four and six months of age.

The safety and immunogenicity of two formulations of an acellular pertussis vaccine as a booster at 17 to 19 months of age were assessed in children immunized at 2, 4 and 6 months of age with acellular or whole cell pertussis vaccine. In Study I 86 children primed with a five-component acellular vaccine combined with diphtheria and tetanus toxoids or with a whole cell pertussis-diphtheria-tetanus vaccine were boosted with the same vaccine. Local reactions (64% vs. 93%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) and systemic reactions (68% vs. 97%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) were less common after the fourth dose of acellular vaccine than after the fourth dose of whole cell vaccine. In Study II 96 children primed with either an acellular or whole cell pertussis vaccine were boosted with an acellular vaccine. Local adverse reactions after booster immunization with acellular vaccine were more common in children primed with acellular vaccine than those primed with whole cell vaccine (68% vs. 33%; relative risk, 2.1; 95% confidence interval, 1.3 to 3.3). Antibody response to pertussis toxin, filamentous hemagglutinin and fimbriae were higher before and 1 month after the booster dose in children primed with the acellular vaccine. We conclude that the acellular pertussis vaccine is safe and immunogenic when used for the booster dose in children primed with either whole cell or acellular vaccine but is associated with local reactions.

Analysis of Variance↗
PubMed1995

Safety and immunogenicity of two acellular pertussis vaccines with different pertussis toxoid and filamentous hemagglutinin content in infants 2-6 months old.

The optimal composition and antigen content of acellular pertussis vaccines is not known. Two vaccines with different quantities of pertussis toxoid (10 and 20 micrograms) and filamentous hemagglutinin (5 and 20 micrograms) and identical 69 kD protein (3 micrograms) and fimbriae 2 and 3 (5 micrograms) combined with diphtheria and tetanus toxoids were compared in a randomized, double-blind study in 2,050 infants undergoing their primary immunization series at 8 centers in the US and Canada. A 6:1 increased antigen to lower antigen allocation was used; 96% of infants received 3 doses and completed the study. A 'clinically significant' local reaction was reported in 3-6% of participants after each dose. Erythema was the most common reaction occurring in 3-5% of infants after the second or third dose. A clinically significant systemic adverse reaction was reported in 28-34% of vaccinees (or vaccinated children) after each dose; fever (7-18%) and fussiness (12-17%) were most common. There were no differences in adverse events between the 2 vaccine formulations. Antibody responses were measured in 292 infants at 1 center. At 7 months, geometric mean anti-filamentous hemagglutinin antibody titers were higher in recipients of the higher antigen content vaccine (p < 0.001) whereas recipients of the lower antigen content formulation had higher anti-fimbriae antibody (p < 0.001) and agglutinin titers (p < 0.05). No differences were detected in anti-pertussis toxin or other antibody responses between the formulations. We conclude that increasing the antigen content of the acellular pertussis vaccine had a variable effect on antibody response but was not associated with increased adverse reactions.

Adhesins, Bacterial↗
PubMed1994

Immunogenicity of a five-component acellular pertussis vaccine in infants and young children.

OBJECTIVE: To compare the reactogenicity and immunogenicity of an acellular vaccine containing pertussis toxoid, filamentous hemagglutinin, and fimbriae 2 and 3, with and without the 69-kd membrane protein, alone or combined with diphtheria and tetanus toxoids. PARTICIPANTS AND SETTING: One hundred thirty-seven 17- to 18-month-old and 22 4- to 6-year-old children who had received three or four previous doses of whole-cell vaccine, respectively, were recruited from public health immunization clinics. DESIGN AND INTERVENTIONS: Three groups of children were sequentially enrolled in the study to receive the acellular pertussis vaccine with or without a 69-kd protein (CP4 or CP5, 17- to 18-month-old children), the two vaccines combined with diphtheria and tetanus toxoids (CP4DT or CP5DT, 17- to 18-month-old children), or the CP5DT vaccine (4- to 6-year-old children). Children were assigned to the first two groups in a randomized and double-blind fashion; the last group was formed by open enrollment. Data regarding adverse reactions were recorded by the parents and collected via a structured interview administered seven times, five times during the first 72 hours. Serum samples were obtained before and 1 month after the immunization, and antibodies against each constituent of the vaccine were measured. RESULTS: A systemic adverse reaction was reported in 40% to 65.7% of 17- to 18-month-old and 38.1% of 4- to 6-year-old children; no severe reactions occurred. A local reaction was reported in 8.6% to 29.4% and 71.4% of children, respectively. No differences were detected between respectively. No differences were detected between vaccines; inclusion of the 69-kd membrane protein did not increase reactogenicity. All vaccines elicited an antibody response to all antigens contained in the formulation. CONCLUSIONS: The five-component acellular pertussis vaccine (Connaught Laboratories Ltd, Willowdale, Ontario) is safe and immunogenic in 17- to 18-month-old and 4- to 6-year-old children. The 69-kd protein was immunogenic, and its inclusion neither increased side effects associated with the vaccine nor adversely affected the antibody response to the other components.

Adhesins, Bacterial↗
PubMed1994

Identification of Bordetella pertussis infection by shared-primer PCR.

A shared-primer PCR method for the detection of infection was developed by using primers derived from DNA sequences upstream of the structural genes for the porin proteins of Bordetella pertussis and Bordetella parapertussis. This method resulted in a 159-bp PCR product specific for B. pertussis and a 121-bp DNA fragment specific for B. parapertussis and allowed for the simultaneous detection of these pathogens. The PCR procedure was shown to be very specific since no PCR product was obtained from 36 non-Bordetella bacterial DNAs. Nasopharyngeal aspirates (NPAs) from children suspected of having pertussis were evaluated by the PCR method, culture, and the Chinese hamster ovary (CHO) cell assay, which detects pertussis toxin. B. pertussis was cultured from 119 of 205 NPAs assayed, and the presence of pertussis toxin was detected in 69 of the NPAs by the CHO cell assay. When ethidium bromide staining was used to detect PCR products, 100 NPAs gave positive results by shared-primer PCR; 94 of these NPAs were also positive by culture. The result indicated a sensitivity of 79% for PCR when culture was used as the standard. The sensitivity of PCR was increased to 95% when a digoxigenin immunoblot system was used. An additional 20 NPAs from patients with suspected pertussis that were culture negative also gave positive results by PCR. The specific and sensitive PCR method described here should be useful for both the clinical diagnosis of pertussis and case identification in vaccine trials.

Animals↗
PubMed1992

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.

Antibodies, Bacterial↗
PubMed1992

Evaluation of a tuberculosis screening program at a children's hospital.

Routine screening of patients for tuberculosis at the time of hospitalization and annual screening of hospital employees continue to be controversial. No data are available concerning tuberculosis screening programs at pediatric facilities. We reviewed the results of patient and employee tuberculosis screening programs in the last decade at the Izaak Walton Killam Hospital for Children. Four (11%) of 37 cases of tuberculosis were unsuspected until identified by the routine screening of all children at their admission to the hospital. No cases of tuberculosis were identified as a result of the employee screening program. Compliance with both screening programs was less than optimal. Review of programs at other Canadian pediatric centers demonstrated a range of practice. We conclude that routine screening of patients at the time of admission to the hospital and the annual screening of employees are unwarranted at present at our children's hospital. However, discontinuation of routine testing necessitates aggressive contact-tracing by public health authorities of patients with identified cases and periodic reevaluation of costs and benefits to determine whether reintroduction of screening is appropriate.

Hospital Bed Capacity, 100 to 299↗
PubMed1991

Epitope specificity of three anti-pertussis toxin monoclonal antibodies with dissimilar effects in assays of toxin neutralizing activity.

The epitope specificity of two monoclonal antibodies against the S1 subunit (A4, A12) and one MAb against the S3 subunit (B9) of pertussis toxin, all protective in the mouse aerosol model of B. pertussis infection, but with different effects in assays of toxin-neutralizing activity, was examined in competitive binding enzyme immunoassays using biotinylated anti-pertussis toxin monoclonal antibodies or biotinylated goat anti-pertussis toxin polyclonal antibody after preincubation with unlabelled antibody. Biotinylated A4 was blocked by A4, A12, and B9; A12 was blocked by A4, A12, and B9. In contrast, biotinylated B9 was blocked by B9 and A4, but not by A12. All three monoclonal antibodies successfully blocked the anti-pertussis toxin polyclonal antibody; a mixture of the three anti-pertussis toxin monoclonal antibodies was more effective than any monoclonal antibody alone P less than or equal to 0.01). These data suggest that these three anti-pertussis toxin monoclonal antibodies recognize separate, but closely linked epitopes on pertussis toxin, and that epitopes on the S1 subunit and B-oligomer may induce protective immunity.

Animals↗
PubMed1991

Modulation of Bordetella pertussis infection with monoclonal antibodies to pertussis toxin.

Three monoclonal antibodies to pertussis toxin were characterized and used to investigate its role in immunity. Antibody affinity correlated with toxin neutralization in in vivo and in vitro assays but was not the only determinant of protection against Bordetella pertussis infection. B9, a high-affinity anti-S3 antibody, was the most effective in neutralizing toxin-induced CHO cell clustering and hemagglutination in vitro and lymphocytosis and histamine sensitization in vivo. A4, a similar-affinity anti-S1 antibody, was less active in the toxin neutralization assays but more protective in the mouse infection model. A12, a low-affinity anti-S1 antibody, was least active in the assays of toxin neutralization but as effective as B9 in the infection model. These data suggest that epitopes on the A protomer and B oligomer may induce protective immunity. Measurement of pertussis toxin neutralization by monoclonal antibodies in in vitro and in vivo assays may not accurately predict protection against infection with B. pertussis.

Animals↗
PubMed1991

Immunization with Haemophilus influenzae type b polysaccharide vaccine at 18 and 24 months of age: evidence of decreased immunogenicity.

In order to assess the immunogenicity of a two-dose regimen of Haemophilus influenzae type b polysaccharide vaccine, the immune response to vaccine given at both 18 and 24 months of age was compared to the response to a single dose at 24 months of age. Following immunization at 24 months of age, the geometric mean antibody concentration of children previously immunized at 18 months (0.53 micrograms/ml) was significantly lower than that of children who received a single dose of vaccine at 24 months (1.03 micrograms/ml; p = 0.03). A four-fold rise in antibody concentration was demonstrated in 31% of children who had received two immunizations and 53% of children immunized for the first time at 24 months of age (p = 0.02). These results suggest that the administration of a dose of plain polysaccharide vaccine at 18 months of age blunted the response to reimmunization at 24 months of age. A subgroup of children who failed to respond to one or two doses of plain polysaccharide vaccine were immunized with polysaccharide-diphtheria toxoid conjugate vaccine. The majority of these children developed a significant rise in antibody concentration in response to conjugate vaccine.

Age Factors↗
PubMed1990

Use of a Chinese hamster ovary cell cytotoxicity assay for the rapid diagnosis of pertussis.

A cytotoxicity assay with Chinese hamster ovary cells (CHO) capable of detecting 750 pg of pertussis toxin was assessed for use as a rapid test for the diagnosis of pertussis and compared with direct immunofluorescence (DFA). With pure bacterial cultures and simulated clinical specimens, the CHO assay detected as few as two colonies of Bordetella pertussis; no cytotoxicity occurred with other respiratory tract microorganisms. Next, nasopharyngeal aspirate secretions and nasopharyngeal cultures harvested after 72 h of incubation from 57 culture-positive and 201 culture-negative patients were examined. The CHO assay with nasopharyngeal secretions was positive in 25 (45%) of 55 culture-positive cases; DFA was positive in 15 (26%) of 57 cases (P = 0.05). The CHO assay with 72-h culture washes was positive in 42 (75%) of 57 culture-positive cases (P less than 0.001 compared with DFA). The CHO assay was more specific than DFA; all five CHO-positive, culture-negative cases were confirmed as true positives by serologic or toxin neutralization assays. In contrast, only 4 (36%) of 11 DFA-positive, culture-negative cases were confirmed as pertussis by serologic methods (P = 0.03). Combining the CHO assay with culture significantly decreased the delay in laboratory diagnosis of pertussis (3.30 versus 4.54 days; P = 0.01). The CHO assay is a sensitive and specific assay for the rapid diagnosis of pertussis.

Animals↗
PubMed1990

Haemophilus influenzae type B and its role in diseases of the head and neck.

Haemophilus influenzae is a common pathogen in infections of the head and neck. Although most mucosal infections (otitis media, sinusitis) are caused by non-encapsulated organisms, invasive disease (meningitis, periorbital cellulitis, epiglottis) is caused by type B encapsulated organisms. Bacteremia is common with H. influenzae type B infections and therapy with parenteral antibiotics is indicated. A vaccine against H. influenzae type B given at 18 months of age is now part of the routine childhood immunization schedule. Chemoprophylaxis with rifampin is recommended for at-risk contacts of patients with invasive type B disease. This review examines the bacteriology, pathogenesis, immunity, and disease manifestations of H. influenzae. Appropriate diagnostic methods, antimicrobial therapy, and recommended chemoprophylaxis and immunoprophylaxis are presented.

Anti-Bacterial Agents↗
PubMed1989

Persistence of pertussis in an immunized population: results of the Nova Scotia Enhanced Pertussis Surveillance Program.

An enhanced pertussis surveillance and laboratory diagnosis program was initiated in the Halifax metropolitan area of Nova Scotia to better delineate the epidemiology of pertussis. During the 28 months of the study, 526 cases of pertussis were identified (overall yearly incidence: 74 cases per 100,000 population). Laboratory confirmation was obtained in 168 (32%) cases, including 111 (21%) by culture. Peak incidence occurred among children 2 to 5 years of age; the highest morbidity rate was seen in children less than 1 year of age. Hospitalization was required for 22 (4.2%) patients; 14 (64%) of those hospitalized were less than 1 year of age. Most (91%) patients had received at least three doses of pertussis vaccine; vaccine efficacy was estimated at 45%. The surveillance program demonstrated that the incidence of pertussis in Nova Scotia, although among the highest in North America, is still underestimated. A ninefold increase in cases was identified over the comparable period of the previous year, largely because patients meeting clinical criteria were reported. By supplementing culture techniques with immunofluorescent staining and serologic methods, we increased the rate of laboratory confirmation from 17% to 65%, suggesting that strict clinical criteria accurately reflect accurately reflect incidence. We conclude that pertussis remains a significant health problem in Nova Scotia, despite nearly universal vaccination.

Child, Preschool↗
PubMed1989

Evaluation of culture, immunofluorescence, and serology for the diagnosis of pertussis.

Nasopharyngeal culture, direct immunofluorescence, and serology of acute-phase and paired serum specimens were compared for the laboratory diagnosis of infections due to Bordetella pertussis in a community-based pediatric population with both high vaccine usage and high pertussis incidence. In 77 (37%) of 210 patients evaluated, one or more tests were positive for pertussis. A clinical illness compatible with pertussis was present in 52 (71%) of 73 pertussis test-positive and 42 (35%) of 119 test-negative patients (P less than 0.001). Nasopharyngeal culture was of low sensitivity (20 [26%] of 77 positive tests) but was most commonly confirmed by another positive pertussis test (85%). Direct immunofluorescence was both insensitive and nonspecific; only 6 (30%) of 20 cases positive by culture were positive by immunofluorescence, and only 4 (33%) of 12 of the culture-negative, immunofluorescence-positive cases could be confirmed by another positive pertussis test. Although serology by enzyme immunoassay proved to be the most sensitive of the laboratory tests (87%), this sensitivity could be achieved only by assaying both acute-phase and paired serum specimens and measuring immunoglobulin G (IgG), IgA, and IgM antibodies to two pertussis antigens (pertussis toxin and filamentous hemagglutinin). Loss of sensitivity occurred with any reduction in the number of these serologic assays performed. Optimal laboratory diagnosis of endemic pertussis in a pediatric population requires both nasopharyngeal culture and serology by enzyme immunoassay.

Antibodies, Bacterial↗
PubMed1988

Experimental respiratory infection with Bordetella pertussis in mice: comparison of two methods.

The mouse respiratory model is being used increasingly to study the pathogenesis and immunology of Bordetella pertussis infection. Two methods of inoculation, aerosol and intranasal, are routinely used to establish the infection. We compared the two methods of inoculation for reproducibility of infection using quantitative lung cultures and distribution of infection with [35S] methionine labeled bacteria and pulmonary histopathology. Ability to produce a respiratory infection intranasally was related to the inoculum volume; a minimum of 20 microliters was required although considerable variability remained. Lung bacterial counts in identically inoculated mice varied 1,000 fold following intranasal inoculation compared to only 5 fold following aerosol inoculation. Distribution of pulmonary 35S-labeled bacteria varied widely (right lung, 43-84%; left lung 16-57%) following intranasal in comparison to aerosol inoculation (right, 60-68%; left 32-40%). Finally, intranasal inoculation produced a scant, patchy, bronchopneumonia whereas diffuse pathology involving all pulmonary segments was seen following aerosol infection. Due to the superior reproducibility and predictable distribution of infection and pathology, aerosol inoculation is the method of choice for establishing the mouse model of pertussis respiratory infection.

Administration, Intranasal↗
PubMed1987

Antibody response to bacteriophage hyaluronidase in acute glomerulonephritis after group A streptococcal infection.

In a test of the hypothesis that lysogeny of group A streptococci by a temperate bacteriophage might confer nephritogenicity, 283 sera from 69 patients were examined for IgG and IgM antibodies to M 49 streptococcal bacteriophage hyaluronidase. The IgG and IgM response to bacteriophage hyaluronidase was greatest in M 49 streptococci-infected individuals with nephritis, but M 49 streptococci-infected subjects without nephritis also had a greater immune response than did subjects infected with serotypes other than M 49. Although antibody to bacterial hyaluronidase was detected in all Streptococcus-infected groups, antibody to M 49 streptococcal bacteriophage hyaluronidase usually was found in only M 49 streptococci-infected patients. Although the greatest IgG and IgM antibody response to bacteriophage hyaluronidase can be demonstrated in individuals with glomerulonephritis, the antibody response does not indicate a direct relation of lysogeny and nephritis because subjects with and without nephritis after M 49 streptococcal infection all had a significant rise in antibody titer.

Antibodies, Bacterial↗