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Biomedical subjects

S M Marcy

Publications and source records attributed to S M Marcy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Vaccine Safety Datalink project: a new tool for improving vaccine safety monitoring in the United States. The Vaccine Safety Datalink Team.

OBJECTIVE: To fill the large "gaps and limitations" in current scientific knowledge of rare vaccine adverse events identified in recent reviews of the Institute of Medicine. METHODS: Computerized information on immunization, medical outcomes, and potential confounders on more than 500 000 children 0 to 6 years of age is linked annually at several health maintenance organizations to create a large cohort for multiple epidemiologic studies of vaccine safety. RESULTS: Analysis of 3 years of follow-up data shows that 549 488 doses of diphtheria-tetanus-pertussis (DTP) and 310 618 doses of measles-mumps-rubella (MMR) vaccines have been administered to children in the study cohort. Analyses for associations between vaccines and 34 medical outcomes are underway. Screening of automated data shows that seizures are associated with receipt of DTP on the same day (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1 to 4.0) and 8 to 14 days after receipt of MMR (RR, 3.0; 95% CI, 2.1 to 4.2). The diversity of vaccination exposures in this large cohort permits us to show that an apparent association of seizures 8 to 14 days after Haemophilus influenzae type b vaccine (RR, 1.6; 95% CI, 1.2 to 2.1) was attributable to confounding by simultaneous MMR vaccination; the association disappears with appropriate adjustment (RR, 1.0; 95% CI, 0.7 to 1.4). CONCLUSION: Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines. The diversity in vaccine administration schedules permits potential disentangling of effects of simultaneous and combined vaccinations. The project provides a model of public health-managed care collaborations in addition to an excellent infrastructure for safety and other studies of vaccines.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group.

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.

Antibodies, Bacterial↗
PubMed1996

Comparative safety and immunogenicity of two recombinant hepatitis B vaccines given to infants at two, four and six months of age.

OBJECTIVES: To evaluate the relative safety and immunogenicity of the two recombinant hepatitis B vaccines licensed in the United States with doses recommended for routine immunization of low risk infants and a schedule that corresponds with routine pediatric visits. METHODS: Healthy infants were immunized at 2, 4 and 6 months of age with hepatitis B vaccine manufactured by either SmithKline Beecham (Engerix-B, 10 micrograms/dose, n = 228) or Merck and Co. (Recombivax HB, 2.5 micrograms/dose, n = 200). Adverse reactions were ascertained by parental reports and interviews and by review of medical records. Antibody concentrations to hepatitis B surface antigen (anti-HBs) were measured in sequential serum specimens by enzyme immunoassay. RESULTS: Adverse reactions were mild and the rates were not significantly different between the two groups. After the first and second doses the rates of seropositivity (> or = 10 mIU/ml) and seroprotection (> or = 10 mIU/ml) were significantly higher in infants given SmithKline Beecham vaccine (P < 0.01). After the second and third doses infants given SmithKline Beecham vaccine also had significantly higher geometric mean anti-HBs concentrations compared with those given Merck vaccine (348.0 mIU/ml vs. 66.9 and 1914.8 mIU/ml vs. 514.8 mIU/ml, respectively, P < 0.001). Nevertheless after the third dose 99% of infants in both vaccine groups achieved seroprotective antibody concentrations. CONCLUSIONS: Both recombinant hepatitis B vaccines were safe and immunogenic when administered concurrently with other pediatric vaccines at 2, 4 and 6 months of age, but earlier protective responses were observed with the SmithKline Beecham vaccine than with the Merck vaccine.

Consumer Product Safety↗
PubMed1995

Enhanced antibody responses in infants given different sequences of heterogeneous Haemophilus influenzae type b conjugate vaccines.

To evaluate the safety and immunogenicity of differing sequences of heterogeneous Haemophilus influenzae type b (Hib) conjugate vaccines, we randomly assigned 300 infants to one of six vaccination schedules. At 2, 4, and 6 months of age, subjects were given single or heterogeneous vaccines: Hib polysaccharide (PRP) conjugated to mutant diphtheria toxin (HbOC), PRP conjugated to outer-membrane protein of Neisseria meningitidis (PRP-OMP), or PRP conjugated to tetanus toxoid (PRP-T). No serious reactions were attributable to immunization with heterogeneous vaccines, and there were few significant differences in the rates of minor adverse reactions among groups. PRP-OMP was the only vaccine that induced an antibody response after the first dose, but significant booster responses were not seen after the second and third doses. Subjects given PRP-T vaccine responded well after two doses, but three doses of HbOC vaccine were needed for an equivalent antibody response. All the Hib vaccine schedules evaluated were immunogenic, and schedules initiated by PRP-OMP vaccine at 2 months of age, followed by two doses of either HbOC or PRP-T vaccine at 4 and 6 months of age, induced the highest antibody levels after each dose. Such schedules may be the best for protecting infants and children who are at greatest risk of having invasive Hib disease, such as American Indian children.

Aging↗
PubMed1991

Pathophysiology of reactions associated with pertussis vaccine.

Many adverse clinical events occur after pertussis immunization in children, but the pathophysiology is not well understood. It has been suggested that some of these adverse events may be due to biologically-active LPF and endotoxin present in DTP vaccines. Fifty-six children were studied who experienced severe reactions (fever greater than or equal to 40.5 degrees C, seizures, persistent crying greater than or equal to 3 hours or hypotonic-hyporesponsive episodes) within 48 hr of DTP immunization. Leukocytosis with neutrophilia was noted acutely (after vaccination) compared to follow-up (approximately one month later). No changes in insulin or glucose values were noted. Utilizing the CHO cell assay, no biologically-active LPF was found in the acute sera of children who had DTP-associated seizures. We found no evidence that biologically-active LPF or altered insulin/glucose metabolism were related to severe DTP-associated reactions.

Blood Glucose↗
PubMed1990

Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children.

We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989. Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30. Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990. Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP. Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination. We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age.

Bacterial Vaccines↗
PubMed1990

Persistence of antibody and booster responses to reimmunization with Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children initially immunized at 15 to 24 months of age.

To evaluate the persistence of antibody after Haemophilus influenzae type b polysaccharide vaccine (PRP) and H influenzae type b polysaccharide diphtheria toxoid conjugate vaccine (PRP-D), a group of 141 infants initially immunized between 15 and 24 months of age were studied 1 year later. One month after immunization with PRP, the man anti-PRP antibody level was 0.27 microgram/mL and 1 year later was 0.29 microgram/mL (not significant). In the group immunized with PRP-D, the levels were 1.34 micrograms/mL and 1.20 micrograms/mL (not significant), respectively. To evaluate immunogenicity and safety of a booster immunization 1 year after initial vaccination, subjects were randomly assigned to receive saline, PRP, or PRP-D. In addition, 73 age-matched previously unimmunized subjects were vaccinated with PRP or PRP-D. In all groups, adverse reactions were minor and resolved by 48 hours. Subjects receiving booster immunization with PRP or PRP-D had significantly greater antibody responses than children of the same age receiving their first dose of vaccine. The highest antibody levels were achieved in children initially immunized with PRP-D, regardless of whether the booster vaccine was PRP (112.8 micrograms/mL) or PRP-D (122.0 micrograms/mL) (not significant). Antibody levels after booster vaccine were significantly lower in those initially given PRP compared with those initially given PRP-D but significantly higher than in age-matched previously unimmunized control subjects (PRP booster 3.16 micrograms/mL vs control of 0.62 microgram/mL [P less than .05]; PRP-D booster 12.31 micrograms/mL vs control 2.31 micrograms/mL [P less than .01]).

Antibody Formation↗
PubMed1989

Analyses of adverse reactions to diphtheria and tetanus toxoids and pertussis vaccine by vaccine lot, endotoxin content, pertussis vaccine potency and percentage of mouse weight gain.

We investigated the rates of local and systemic reactions following 9920 diphtheria-tetanus toxoids-pertussis immunizations from 25 lots of commercially available, United States-licensed diphtheria-tetanus toxoids-pertussis adsorbed vaccines from four manufacturers as a function of vaccine lot, endotoxin content, pertussis vaccine potency and percent of mouse weight gain. There were significant differences between the rates of reactions by lot for all local and systemic reactions except convulsions and hypotonic hyporesponsive episodes. For these latter reactions there were insufficient cases for analyses. P was less than 0.0001 for local reactions, fever, drowsiness, fretfulness, anorexia and screaming and 0.017 for vomiting. No single lot was associated with the highest or lowest rate of reactions for more than 3 of the 11 reactions. There was a significant positive association of endotoxin unit (EU) content and the percent of vaccine recipients who developed fever (P = 0.004). Fever increased in frequency from 20.6% of children immunized with vaccine lots that contained 2500 EU to 55.1% of children immunized with vaccine lots containing 40,000 EU. There were significant positive associations of all local reactions and pertussis vaccine potency (P = 0.0004), and percent of mouse weight gain (P less than 0.0001). There was also a positive association of percent mouse weight gain and persistent screaming (P = 0.001). However, for the majority of reactions there was no clinically meaningful associations between reaction rates and the biological properties of the vaccine studied.

Animals↗
PubMed1988

Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation.

In a prior prospective study, we evaluated the nature and rates of adverse reactions occurring within 48 hours following 15,752 diphtheria-tetanus-pertussis (DTP) immunizations. Nine children had convulsions, and nine had hypotonic-hyporesponsive episodes. After an interval of 6 to 7 years, we were successful in contacting the families of 16 of these children to determine whether any had evidence of neurologic impairment too subtle to have been detected at the time of initial evaluation. All 16 were considered normal by their parents and were doing well in school. A complete neurologic and psychometric evaluation was performed on 13 of these children. No child had significant neurologic deficit, although four had minor neurologic abnormalities. Psychometric testing revealed normal performance IQ scores (104.3 +/- 15.8) but low verbal IQ scores (91.8 +/- 18.4); however, these lower verbal IQ scores can be explained by the proportion of Hispanic and bilingual children in this sample. Therefore, there is no evidence that any of these 16 children have any serious neurologic damage as a result of a convulsion or a hypotonic-hyporesponsive episode temporally associated with a prior diphtheria-tetanus-pertussis immunization.

Child, Preschool↗
PubMed1987

Factors influencing immunogenicity and safety of two Haemophilus influenzae type b polysaccharide vaccines in children 18 and 24 months of age.

The purpose of this study was to evaluate differences in the safety and immunogenicity of Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine produced by two manufacturers (Connaught and Praxis) in children 18 and 24 months of age. Eighty-five children were evaluated in a prospective, double-blind, randomized fashion. Postvaccination antibody concentrations (measured by radioimmunoassay) and response rates were not significantly different between the two manufacturers' vaccines but immunogenicity was significantly less in 18-month-old children (antibody concentration, 0.149 microgram/ml) compared with 24-month-old children (0.838 microgram/ml) (P = 0.001). No significant differences were noted in the safety of the two vaccines. This study suggests that previously observed differences of immunogenicity data between various type b capsular polysaccharide vaccines are due to differences in antibody assays, not in vaccines. Eighteen-month-old children appear to have a relatively poor immune response to type b capsular polysaccharide. Therefore to optimize the benefits of immunization, we suggest children receive this vaccine at 24 months of age.

Age Factors↗
PubMed1985

DTP vaccine reactions: effect of prior reactions on rate of subsequent reactions.

It is generally presumed that children who have had reactions to diphtheria-tetanus-pertussis (DTP) immunization will be more likely to have similar reactions or more severe reactions upon subsequent immunization. To evaluate this contention, we studied the rates of selected reactions occurring within 48 hours of primary DTP immunization in 1,241 infants less than one year of age. Both local and systemic reactions were significantly more frequent following subsequent DTP immunization if present following a prior immunization. The rates of local reactions following subsequent DTP immunization as a function of previous reactions were as follows (no prior reactions/prior reaction): local redness greater than or equal to 2.5 cm, 12.5%/25.5% (p less than 0.0001); local swelling greater than or equal to 2.5 cm, 16.8%/29.0% (p less than 0.0001); local pain, 37.4%/56.4%; (p less than 0.0001). The rates of systemic reactions as a function of previous reactions were as follows (no prior reactions/prior reaction): drowsiness, 24.9%/42.8% (p less than 0.0001); fretfulness, 47.5%/64.7% (p less than 0.0001); vomiting, 4.8%/11.2% (p = 0.0084); anorexia 16.0%/26.3% (p = 0.0001); fever greater than or equal to 38 degrees C, 37.6%/58.5% (p less than) 0.0001); persistent crying, 2.6%/4.5% (p = 0.3557). In addition, infants who experienced a fever greater than or equal to 38 degrees C on the first of two immunizations were more likely to have a temperature greater than or equal to 39 degrees C following the second immunization, 4.2% vs. 12.4% (p = 0.0017). These data strongly support the presumption that children who have had previous reactions following DTP immunization are more likely to have similar reactions upon subsequent immunization.

Anorexia↗
PubMed1981

Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children.

In 784 DT and 15,752 DTP immunizations given to children 0 to 6 years of age who were prospectively studied for reactions occurring within 48 hours following immunization, minor reactions were significantly more frequent following DTP vaccine. The ratio of reaction rates associated with DTP and DT immunizations (DTP/DT) for selected local and systemic reactions was as follows: local redness, 37.4%/7.6%; local swelling, 40.7%/7.6%; pain, 50.9%/9.9%; fever, 31.5%/14.9%; drowsiness, 31.5%/14.9%; fretfulness, 53.4%/22.6%; vomiting, 6.2%/2.6%; anorexia, 20.9%/7.0% and persistent crying, 3.1%/0.7%. Following DTP immunization nine children developed convulsions and nine developed hypotonic hyporesponsive episodes. No sequelae were detected following these reactions.

Child↗