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Biomedical subjects

M C Steinhoff

Publications and source records attributed to M C Steinhoff.

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

A randomized comparison of reactogenicity and immunogenicity of two whole-cell pertussis vaccines.

OBJECTIVE: To compare prospectively the reactogenicity and immunogenicity of two licensed whole-cell pertussis vaccines. METHODS: We conducted a prospective, randomized, double-blinded assessment of two licensed whole-cell pertussis vaccines with diphtheria and tetanus toxoids that were included in a multicenter trial evaluating 13 acellular pertussis vaccines. Infants were immunized at 2, 4, and 6 months of age with a single lot of Lederle (309 infants) or Massachusetts Public Health Biologic Laboratories (MPHBL; 94 infants) vaccine. RESULTS: The group receiving the Lederle vaccine demonstrated significantly higher antibody titers to pertussis toxin by enzyme-linked immunosorbent assay (ELISA) and by the Chinese hamster ovary cell pertussis toxin neutralization assay, and to fimbrial antigens by ELISA, as well as higher mean agglutinin titers. In contrast, the group receiving the MPHBL vaccine demonstrated higher ELISA antibody levels to filamentous hemagglutinin and pertactin. Similar differences were observed in the proportions of vaccinees seroconverting to these antigens. Rates of systemic and local reactions were relatively low for both vaccines. Although the Lederle product had substantially lower reactogenicity in this study than previously reported for that vaccine, the MPHBL vaccine was significantly less reactogenic in nearly all clinical categories. CONCLUSION: The two whole-cell vaccines demonstrated statistically significant differences in postimmunization antibody levels to all six evaluated pertussis antigens. Whether these statistically significant differences in antibody levels have clinical relevance is not clear. Rates of nearly all local and systemic reactions were significantly lower among the MPHBL group than the Lederle group. Licensed whole-cell diphtheria-tetanus-pertussis vaccines produced by different manufacturers cannot be assumed to be similar in reactogenicity or immunogenicity.

Antibodies, Bacterial↗
PubMed1995

Simultaneous administration of Haemophilus influenzae type b vaccine with acellular or whole-cell pertussis vaccine: effects on reactogenicity and immune responses to pertussis vaccines.

OBJECTIVE: To evaluate the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. METHODS: Enrollment of infants into a large multicenter study of the safety and immunogenicity of 13 DTaP and 2 DTP vaccines was partially completed when the first Hib vaccine, HbOC (Haemophilus b oligosaccharide conjugate vaccine), was licensed for use in infants. Thereafter, at each immunization most infants received HbOC simultaneously with DTaP (or DTP), administered in opposite thighs. Postvaccination geometric mean titers or concentrations (GMTs) of pertussis antibodies as measured by six different assays were compared pairwise among groups of infants receiving 0, 1, 2, or 3 simultaneous HbOC immunizations. The incidence of reactions was compared between infants who received only DTaP or DTP and those who received HbOC simultaneously. RESULTS: Comparison of postvaccination GMTs was possible among groups of infants receiving different numbers of simultaneous immunizations for 10 of the 13 DTaP and both DTP vaccines. Increased HbOC exposure had no consistent dose-response effect on antibody titers for DTaP or DTP vaccines in any assay. Significant differences between groups in postvaccination GMTs were observed with 4 DTaP vaccines in 1 to 2 assays each; the GMTs were higher with increasing HbOC exposure for 2 DTaP vaccines and lower for 2 others. There was no significant increase in reactions with simultaneous HbOC and DTaP immunization. CONCLUSIONS: Based on these retrospective analyses, there did not seem to be an interference in pertussis immunogenicity or alteration in reactogenicity associated with the simultaneous administration of HbOC and DTaP. These findings are encouraging with respect to the development of DTaP-Hib combination vaccines.

Bacterial Proteins↗
PubMed1995

The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids.

OBJECTIVE: To evaluate the effect of maternally derived antibody on the immunogenicity and reactogenicity of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: A total of 2342 infants were randomized to receive one of 13 DTaP or 2 DTP vaccines at 2, 4, and 6 months of age. The correlation between preimmunization and postimmunization antibody after three doses of vaccine and the relation between preimmunization antibody and adverse reactions after the first immunization were modeled by linear regression. RESULTS: After DTP but not DTaP, higher levels of preexisting antibody were associated with substantial (28% to 56%) reductions in the subsequent antibody response to pertussis toxin (PT). For other pertussis antibodies, modest inverse correlations were seen between preexisting antibody concentrations and most postimmunization antibody responses (resulting in 8% to 18% reductions in postimmunization antibody) for both DTP and DTaP. There was no consistent association in any DTP or DTaP group between adverse reactions and preimmunization antibody levels. CONCLUSION: The PT antibody response to DTaP, unlike DTP, is not adversely affected by preexisting antibody to PT. Inhibitory effects with respect to other antibodies, seen with both DTP and DTaP, were relatively modest. Our data suggest that the use of acellular pertussis vaccines in adults, which could confer higher levels of antibody in women before pregnancy, would be unlikely to adversely affect pertussis antibody responses after DTaP among infants born to mothers with high antibody levels.

Antibodies, Bacterial↗
PubMed1995

Effect of gender, race, and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines.

OBJECTIVE: To determine whether gender, race (black or white), or level of parental education influenced serologic responses or reporting of clinical reactions after immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: Healthy infants were prospectively randomized to receive one of 13 DTaP, Lederle DTP, or another DTP. Parents recorded the occurrence of adverse reactions for 2 weeks after each inoculation. Sera obtained before the first immunization and 1 month after the third immunization were analyzed for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin (PRN). Chinese hamster ovary cell pertussis toxin neutralization assays were performed, and levels of agglutinating antibodies determined. RESULTS: Prevaccination antibody levels did not differ by race, gender, or parental education. Postimmunization geometric mean titers (GMTs) were strongly and consistently associated with race. For both DTaP and DTP and for every included antigen, postimmunization GMTs were about twice as high for black as for white infants. Among DTaP recipients, these differences were significant for pertussis toxin, Chinese hamster ovary cell pertussis toxin neutralization assay, filamentous hemagglutinin, PRN, and agglutinins; among the much smaller sample of WCL recipients, the differences achieved or approached statistical significance for agglutinins, PRN, and fimbriae. These findings were confirmed by regression analyses that controlled for gender, parental education, study site, and preimmunization antibody level. Reported reactions were not correlated with parental education level and showed no material correlation with gender. Black infants were reported to have had more pain than white infants after receiving WCL and DTaP and were reported to be more fussy after receiving WCL. CONCLUSIONS: The consistently higher postimmunization GMTs among black infants seems to be a real finding for which we have no explanation; the infants did not significantly differ by race in vaccine assignment, preimmunization antibody levels, age at immunization, or interval from immunization to phlebotomy. These observations should be confirmed and further evaluated in future pertussis vaccine trials. Reported differences by race in pain and fussiness after receiving WCL might reflect chance, differences by race in the occurrence of reactions, or differences by race in the reporting of reactions.

Antibodies, Bacterial↗
PubMed1995

Defining the key parameters for comparing reactions among acellular and whole-cell pertussis vaccines.

OBJECTIVE: To facilitate future vaccine reaction data collection and analysis, we sought to determine the minimum data set required to describe accurately and to compare common reactions after the administration of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: Thirteen DTaP and 2 DTP vaccines were studied in a multicenter trial involving 2342 infants who received a primary series of vaccinations at 2, 4, and 6 months of age. Temperature, fussiness, redness, swelling and pain at the injection site, antipyretic use, drowsiness, loss of appetite, and vomiting were evaluated. Reactions were assessed at 3 hours and (if not immunized in the evening) 6 hours after immunization, at bedtime each evening for 7 evenings, and on the 14th evening after immunization. RESULTS: Two reaction assessment approaches were compared: (1) analysis of all reactions, regardless of the degree of severity; and (2) a condensation of the data to five key reactions (fever > 100 degrees F, moderate or more fussiness, any local redness, any local swelling, and moderate or more local pain). We found that the onset of reactions was infrequent beyond the second evening, and that collection and analysis of reaction data beyond that time did not further discriminate among the vaccines. Information regarding antipyretic use, loss of appetite, drowsiness, or vomiting did not assist in differentiating among these vaccines. CONCLUSION: Monitoring the occurrence of fever greater than 100 degrees F, moderate or severe fussiness, injection site redness or swelling, and moderate or severe injection site pain occurring through the second evening after immunization will provide the minimum data set needed to discriminate among DTaP and DTP vaccines with respect to the common adverse reactions.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

Association of reactions after consecutive acellular or whole-cell pertussis vaccine immunizations.

OBJECTIVE: To evaluate the relative frequency of adverse reactions after initial and subsequent immunizations among infants receiving primary immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus combined. METHODS: We examined the occurrence of common reactions in 2127 infants within 48 hours after immunization at 2, 4, and 6 months with one of 13 DTaP or with Lederle DTP (WCL). Data on at least two consecutive immunizations were available for 357 WCL recipients and 1770 DTaP recipients. For these analyses, reactions evaluated included fever of 100.4 degrees F (38 degrees C) or greater, redness of 21 mm or larger, swelling of 21 mm or larger, moderate or severe pain, moderate or severe fussiness, loss of appetite, drowsiness, and vomiting. RESULTS: With one exception, reactions were approximately 1.5 to 8 times more likely to occur in WCL recipients if the same reaction had been observed at the previous immunization (the single exception was redness after the second immunization). Both initial and repeated reactions were less likely in DTaP than in WCL recipients. As with WCL recipients, risks of repeated reactions in DTaP recipients were higher than the risks of initial reactions (from 2.5 to 24 times as high). CONCLUSION: Reactions after a second or third immunization with either WCL or DTaP vaccine are more likely to occur in infants who had the same reaction after the preceding immunization. Absolute risks of repeated reactions tended to be lower after DTaP vaccine than after the WCL vaccine.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

The reverse cumulative distribution plot: a graphic method for exploratory analysis of antibody data.

Serologic data often have a wide range and commonly do not approximate a normal distribution. Means, medians, SDs, or other conventional numerical summaries of antibody data may not adequately or fully describe these complex data. The reverse cumulative distribution plot is a graphic tool that completely displays all the data, allows a rapid visual assessment of important details of the distribution, and simplifies comparison of distributions.

Antibodies↗
PubMed1995

C substance--specific latex agglutination for early & rapid detection of Streptococcus pneumoniae in blood cultures.

A slide agglutination test was developed using latex particles coated with antiserum against the C substance, a common antigen for all serotypes of Streptococcus pneumoniae. This test was used for the rapid identification of pneumococci in blood culture broths which contained Gram positive cocci (GPC) in pairs or short chains on smear examination. Of 238 consecutive blood cultures with GPC tested, 72 were positive for Strep. pneumoniae by the latex test and conventional methods. The remaining 166 cultures were negative for both these, indicating a 100 per cent specificity and sensitivity for the test.

Antigens, Bacterial↗
PubMed1994

A cluster of invasive pneumococcal disease in young children in child care.

OBJECTIVE: To investigate a cluster of invasive pneumococcal disease in children 8 to 26 months of age, using standard microbiological procedures and ribosomal DNA gene-restriction patterns to characterize the outbreak strain. DESIGN: Outbreak investigation. SETTING: A family child-care home with six children in Baltimore, Md. RESULTS: During an 8-day period, three of the six children in the family child-care home had febrile illnesses with pneumococcal bacteremia, and a fourth had purulent pneumococcal conjunctivitis. Type 12F Streptococcus pneumoniae was isolated from the four ill children and from the nasopharynges of the two healthy children. Ribotyping revealed all outbreak isolates had an identical ribotype pattern. Administration of rifampin to the children did not eradicate carriage of the organism. CONCLUSIONS: Our data demonstrate that child care provides an opportunity for outbreak of invasive pneumococcal disease in young children. This observation suggests a need for increased alertness for clusters of pneumococcal disease in young children in child-care facilities and underscores the necessity for a pneumococcal vaccine that is effective in infants and young children.

Bacteremia↗
PubMed1994

Potential of polymer microencapsulation technology for vaccine innovation.

Biodegradable polymer microspheres or microcapsules developed over the past decade for reliable, preprogrammed release of contraceptive steroids have significant potential for adaptation to antigen release for immunization. In addition, polymeric encapsulation of antigens could prevent the acid and enzymatic degradation that has been a barrier to the development of oral vaccines. This review summarizes the published experience with microencapsulated hormones and antigens, describes the process of microsphere production, discusses the strengths and weaknesses of this approach to immunization, and outlines the gaps in knowledge. Microsphere technology has the potential benefits of reducing the number of inoculations, enhancing the immune response via both parenteral and oral vaccination routes, and in reducing the total antigen dose required to achieve immune protection.

Animals↗
PubMed1994

Serotypes of Streptococcus pneumoniae causing meningitis in southern India. Use of new direct latex agglutination antigen detection tests in cerebrospinal fluid.

The utility of a new latex agglutination (LA) test to directly determine serotypes of Streptococcus pneumoniae in cerebrospinal fluid (CSF) was assessed in prospective evaluation at a referral hospital in southern India. Samples from 18 ill patients with Gram-positive organisms in CSF were tested. The presence of C polysaccharide or specific serotype antigen (types 1, 3, 4, 5, 6, 12, 14, 18, 19, and 23) of S. pneumoniae was detected by slide LA test. Pneumococcal antigen was detected in 17 (94%) of 18 CSF specimens; in 14 (78%) the serotype was determined directly. Serotypes 1, 5, 6, 19, 23, 7, 10, 34, and 38 were found in these patients. A quellung test of the cultured isolates confirmed the serotypes. Information regarding the serotype distribution of pneumococci in varied geographic locations is important for the design and evaluation of pneumococcal vaccines. The slide LA tests seemed useful in detecting S. pneumoniae antigens and in determining the serotype, and have promise in simplifying the gathering of serotype data.

Adult↗
PubMed1994

A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children: effect of polysaccharide size and linkage characteristics.

Because most childhood invasive pneumococcal disease occurs before the age of 2 years, the development of a pneumococcal vaccine that is immunogenic in infants is a priority. We assessed the safety and serum antibody responses to two dose levels of three bivalent pneumococcal capsular polysaccharide (CPS)-protein conjugate vaccines incorporating the poorly immunogenic serotypes 6A and 23F. The conjugate vaccines differed in CPS size and chemical linkage, but all used a nontoxic cross-reactive mutant diphtheria toxin (CRM197) as the protein carrier. 118 young children 18 to 30 months of age received a single immunization with one of the three glycoconjugates or with licensed pneumococcal vaccine. Sera were obtained before and 1 month after immunization and analyzed by enzyme-linked immunosorbent assay for serotype-specific antibody titers. The 23F CPS was more immunogenic than the 6A CPS in all vaccine formats. The most immunogenic 23F conjugate vaccine consisted of native CPS directly linked to the carrier protein; smaller CPS or the use of a six-carbon linker did not appear to enhance immunogenicity in these young children. Conjugation of two pneumococcal CPSs is associated with an increase in immunogenicity, and the characteristics of the CPS and of the CPS-protein linkage appear to influence the antibody response.

Bacterial Vaccines↗
PubMed1994

Use of PCR-enzyme immunoassay for identification of influenza A virus matrix RNA in clinical samples negative for cultivable virus.

Influenza A virus infections are a major cause of morbidity and mortality worldwide. Standard diagnostic methods either are not efficient in identifying infected individuals in a timely manner or lack sensitivity. We developed a PCR-enzyme immunoassay (PCR-EIA) for the detection of influenza A virus RNA in respiratory secretions. A reverse transcription PCR was performed with oligonucleotide primers directed at a highly conserved area of the influenza A matrix gene. Amplified DNA was identified by hybridization in solution to a nested biotinylated RNA probe and quantitated in an EIA. PCR-EIA detected small quantities of RNA from the three prevalent subtypes of human influenza A virus. Influenza B and C, parainfluenza, measles, mumps, and respiratory syncytial viruses tested negative. The potential efficiency of PCR-EIA for use in clinical diagnosis was determined by testing 90 nasal wash specimens obtained daily over a 10-day period from nine human volunteers infected with influenza A virus. Thirty-seven of the postinfection samples had detectable influenza A virus RNA by PCR-EIA, whereas only 26 postinfection samples were positive by culture. PCR-EIA was particularly efficient for the identification of influenza A virus in samples obtained more than 4 days after infection. Seventeen of 45 such samples were positive, whereas virus was cultivated from 4 samples (P < 0.00005). All preinfection samples from volunteers subsequently infected with influenza A virus were negative by PCR-EIA, as were samples from a volunteer infected with parainfluenza virus type 3. Nucleic acid amplification techniques represent important tools for the timely and sensitive diagnosis of influenza A virus infections and, therefore, their management and control.

Base Sequence↗
PubMed1994

Acellular and whole-cell pertussis vaccines as booster doses: a multicenter study.

OBJECTIVE: To compare the safety and immunogenicity of a variety of acellular (AC) and whole-cell (WC) pertussis vaccines combined with diphtheria and tetanus toxoids. METHODS: Standard enrollment and reaction forms were used at five sites, and serologic evaluation was performed at a single site. Nine AC (Massachusetts Public Health Laboratories, Biocine Sclavo recombinant pertussis toxoid [PT], Connaught/BIKEN, Lederle three-component, Biocine Sclavo recombinant three-component, SmithKline Beecham three-component, Porton three-component, Takeda-Wyeth, and Connaught multicomponent), and three WC (Connaught Laboratories, Lederle Laboratories, and Massachusetts Public Health Laboratories) were studied. All AC contained varying concentrations of PT; some vaccines also contained filamentous hemagglutinin (FHA), pertactin, and/or agglutinogens. RESULTS: Two hundred forty children, aged 16 to 21 months and 4 to 6 years, were enrolled at five sites. Significantly less fever, redness, swelling, pain, limp, and use of pain medication were noted following AC compared with WC. Significant increases in antibody to PT were seen following all vaccines. Significant rises in FHA antibody were seen following all WC and the seven AC that contained FHA. Postbooster PT antibody levels were similar among the AC groups, regardless of the amount of PT administered (between 3.5 and 25 micrograms per dose). The dose of FHA did not affect PT antibody response. Infants primed with WC who were boosted with a monocomponent PT vaccine did not manifest a significant antibody response to FHA. CONCLUSION: The rate of adverse reactions was not a function of the number of antigens or the antigen quantity in the acellular vaccines, and antibody responses following AC were similar or better than antibody responses following WC. These results support the further evaluation of these vaccines in a larger National Institute of Allergy and Infectious Diseases-sponsored study in infants.

Antibodies, Bacterial↗
PubMed1993

Hypoxaemia in young Kenyan children with acute lower respiratory infection.

OBJECTIVES: To determine the prevalence, clinical correlates, and outcome of hypoxaemia in acutely ill children with respiratory symptoms. DESIGN: Prospective observational study. SETTING: Paediatric casualty ward of a referral hospital at 1670 m altitude in Nairobi, Kenya. SUBJECTS: 256 Infants and children under 3 years of age with symptoms of respiratory infection. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as arterial oxygen saturation < 90% determined by pulse oximetry, and condition of patient on the fifth day after admission. RESULTS: Over half (151) of the children were hypoxaemic, and short term mortality was 4.3 times greater in these children. In contrast, the relative risk of a fatal outcome in children with radiographic pneumonia was only 1.03 times that of children without radiographic pneumonia. A logistic regression model showed that in 3-11 month old infants a respiratory rate > or = 70/min, grunting, and retractions were the best independent clinical signs for the prediction of hypoxaemia. In the older children a respiratory rate of > or = 60/min was the single best clinical predictor of hypoxaemia. The presence of hypoxaemia predicted radiographic pneumonia with a sensitivity of 71% and specificity of 55%. CONCLUSIONS: Over half the children presenting to this referral hospital with respiratory symptoms were hypoxaemic. A group of specific clinical signs seem useful in predicting hypoxaemia. The clear association of hypoxaemia with mortality suggests that the detection and effective treatment of hypoxaemia are important aspects of the clinical management of acute infections of the lower respiratory tract in children in hospital in developing regions.

Acute Disease↗
PubMed1993

Effect of heterosubtypic immunity on infection with attenuated influenza A virus vaccines in young children.

Resistance to infection with an influenza A virus conferred by previous infection with an influenza A virus belonging to another subtype is called heterosubtypic immunity. Heterosubtypic immunity is demonstrable in laboratory animals but is believed to be weak in humans. The present study examined whether heterosubtypic immunity from previous influenza virus infection induced resistance to infection with an attenuated influenza A vaccine virus. Two groups of vaccinees consisting of young infants and children who received either influenza A H1N1 or H3N2 attenuated virus were studied. Influenza A H3N2 virus vaccine recipients were classified by their preexisting H1N1 heterosubtypic antibody level induced by prior infection with wild-type virus, and the H1N1 vaccinees were classified by their history of infection with H3N2 vaccine virus. For both groups of vaccinees, the rates of seroconversion and virus shedding and the level of vaccine virus replication were compared in subjects with and without heterosubtypic immunity. In 48 influenza A H3N2 virus and 39 H1N1 virus vaccinees, heterosubtypic immunity had no demonstrable effect on infectivity, immunogenicity, or replication of attenuated vaccine virus. These observations confirm the weak nature of heterosubtypic immunity in humans and suggest that it will not limit the utility of live attenuated influenza A viruses in young infants and children.

Antibodies, Viral↗
PubMed1991

Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines. METHODS: We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H. influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM). The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55). RESULTS: Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter). In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01). However, the subjects with AIDS had a greater antibody response to the PRP vaccine. The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine). In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV. CONCLUSIONS: Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H. influenzae type b.

AIDS Vaccines↗