Duration of serum antibodies elicited by Haemophilus influenzae type b capsular polysaccharide alone or conjugated to tetanus toxoid in 18- to 23-month-old children.
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Aluminum Hydroxide↗
Biomedical subjects
B Trollfors
Publications and source records attributed to B Trollfors.
Immunogenicity and safety of a pertussis vaccine composed of pertussis toxin inactivated by hydrogen peroxide, in 18- to 23-month-old children.
A new pertussis vaccine, composed of purified pertussis toxin inactivated by hydrogen peroxide and adsorbed onto aluminum hydroxide (NICHD-Ptxd), was injected into 60 children aged 18 to 23 months without a history of pertussis or pertussis vaccination. Two doses of toxoid, 10 and 50 micrograms, were used. Two injections, given 8 to 12 weeks apart, elicited increases in serum levels of antitoxin and IgG antibodies in 56 children who had no detectable antitoxin (less than 5 units) before vaccination. Four children with detectable antitoxin (greater than or equal to 5 units) before the first vaccination had pronounced antibody increases after the first dose. After the second dose, the geometric mean antitoxin concentration was 29 units with the 50 micrograms dosage and 10 units with the 10 micrograms dosage (p less than 0.001). Serum antibody levels elicited by two injections of 50 micrograms were similar to those in patients convalescing from pertussis. A third injection given to seven children 9 to 10 months after the second injection gave a booster response, with high levels of antitoxin (160 to 1280 units) and of IgG antibodies. With few exceptions the antibody response was restricted to the IgG class. Transient local reactions greater than or equal to 2 cm in diameter occurred in 14% of the children after the first dose and in 44% after the second and third doses. Moderate fever was recorded after 6% of all injections. There were no changes in peripheral blood leukocyte counts or fasting blood glucose levels measured before and 24 hours after the first injection. We conclude that NICHD-Ptxd is immunogenic in children. No serious adverse effects were noted.
Antibodies, Bacterial↗
History of whooping cough in nonvaccinated Swedish children, related to serum antibodies to pertussis toxin and filamentous hemagglutinin.
The aim of this study was to examine whether there is a correlation between parental information on the child's history of whooping cough and the presence or absence of serum antibodies against two antigens of Bordetella pertussis, pertussis toxin and filamentous hemagglutinin, in nonvaccinated Swedish children. The parents of 266 Swedish children aged 1 to 4 years answered a questionnaire regarding the child's history of whooping cough, and a serum sample was obtained from the child for determination of IgG, IgM, and IgA antibodies to pertussis toxin and filamentous hemagglutinin. The study was performed from 1984 to 1986, five to seven years after the cessation of general vaccination against pertussis in Sweden; none of the children had received pertussis vaccine. Antibodies to both toxin and filamentous hemagglutinin increased with age. Of the children aged 4 years, 50% had antibodies to both antigens. Of all 266 children, 100 had antibodies to both antigens, 6 to toxin alone, and 49 to filamentous hemagglutinin alone. There was a good correlation between the presence of antibodies and a history of whooping cough. Of 91 children with a history of whooping cough, 77 had antibodies against both antigens and 13 against one antigen; only one child lacked detectable antibodies against both antigens. Of the 175 children with no history of whooping cough, 110 lacked detectable antibodies to both antigens, 23 had antibodies to both, 2 to toxin alone, and 40 to filamentous hemagglutinin alone. The data indicate that parental information on a previous history of whooping cough in their nonimmunized child is reliable, and that many infections with B. pertussis are subclinical or atypical. Exposure to other Bordetella species than B. pertussis, which is the only toxin-producing species, might be important for the development of FHA antibodies. A follow-up 2 to 4 years after the collection of serum samples of children without a history of whooping cough but with antibodies to one or both antigens indicated that serum antibodies to toxin, but not to filamentous hemagglutinin, may be protective against disease.
Age Factors↗
Glomerular filtration rate and tubular involvement during acute disease and convalescence in patients with nephropathia epidemica.
Glomerular filtration rate (GFR) and tubular involvement were studied in 74 patients with serologically verified nephropathia epidemica (NE). Increased levels of serum creatinine and serum beta 2-microglobulin were documented in 96% and 99% of the patients, respectively. The mean of the lowest estimated GFR was 26 ml/min. Proximal tubular reabsorptive capacity was assessed by urinary loss of beta 2-microglobulin and cell damage by urinary activity of N-acetyl-beta-D-glucosaminidase. Both of these parameters were elevated in most of the patients during the acute phase of the disease. Increased serum levels of Tamm-Horsfall-specific IgG and/or IgA occurred in 72 of 74 patients. No patient required dialysis and there was no mortality. Six months after discharge only three patients had a GFR less than 80 ml/min as estimated by [51Cr]EDTA clearance; two of these had underlying chronic diseases and one had suffered clinically severe NE. Desmopressin tests showed decreased urine osmolarity in three patients 8 months after discharge. These three had chronic diseases, which may have contributed to the impaired tubular function. Thus, there was a markedly decreased GFR and a tubular dysfunction in the acute phase of NE. Most patients recovered within a few months and none showed evidence of chronically impaired renal function due to NE.
Acetylglucosaminidase↗
Incidence and etiology of neonatal septicaemia and meningitis in western Sweden 1975-1986.
In a retrospective study of neonatal septicaemia and meningitis in a defined region of western Sweden 1975-1986, 231 cases were identified. The incidence was 2.8/1000 live births. The case-fatality rate was 15%. thirty-three patients had meningitis. Only 55 patients (24%) had no known risk factors. Preterm delivery was a most important risk factor for both morbidity and mortality. The most common causative organisms were group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods, together isolated from 82% of the patients. The cases were approximately equally divided between very early, early and late onset infections. Group B streptococci were over-represented in very early onset infections in all birthweight groups and aerobic Gram-negative rods were the most common isolates from low birthweight infants with late onset infections. However, group B streptococci, Staphylococcus aureus and Gram-negative rods were found in all birthweight and gestational age groups. Thus, initial antimicrobial therapy must be equally broad in all neonates with suspected septicaemia.
Female↗
Immunoglobulin A antibodies to pertussis toxin and filamentous hemagglutinin in saliva from patients with pertussis.
Immunoglobulin A (IgA) antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 181 saliva samples obtained during various stages of pertussis from 112 patients were determined. Saliva samples obtained within 5 days after the onset of symptoms did not have detectable IgA antibodies against either of the two antigens. Of the samples obtained between 6 and 50 days after the onset of symptoms, 72% had antibodies against FHA but only 40% had antibodies against PT. With few exceptions, saliva samples obtained more than 50 days after the onset of symptoms contained antibodies against both antigens. In the 59 patients from whom paired saliva samples were obtained at intervals of 2 to 5 weeks, a significant increase in the geometric mean FHA antibody titers but not PT antibody titers occurred. However, increases that were fourfold or greater were observed against FHA in only 19 patients and against PT in 14 patients. Thus, IgA antibodies against FHA and PT in saliva develop during pertussis, and the importance of secretory IgA antibodies for protection against infection and disease should be investigated. Determination of these antibodies in paired saliva samples is, however, of little value for the laboratory diagnosis of pertussis.
Adolescent↗
Acute epiglottitis in children and adults in Sweden 1981-3.
In a retrospective study of the incidence of acute epiglottitis in Sweden, 485 children and 356 adults fulfilled the following criteria: (a) red and swollen epiglottis visualised at laryngoscopy; (b) stridor or difficulties in swallowing own saliva or water; and (c) temperature greater than or equal to 38 degrees C. The age specific incidence in children (0-14 years) was 10 and in adults (greater than or equal to 15 years) 1.8/100,000/year. These incidence rates were higher than the incidence of Haemophilus influenzae meningitis in the same population. Blood cultures were obtained from 290 children (60%) and 185 adults (52%). H influenzae was isolated from 267 blood cultures (92%) from children and 98 blood cultures from adults (53%). Other organisms were isolated from six adults (3%). An artificial airway was established in 352 children (73%) and in 68 adults (19%); the remainder were treated conservatively. Six children and two adults died. Sweden has a high incidence of acute epiglottitis in children and the disease also occurs in adults. The importance of H influenzae in the aetiology of epiglottitis in all age groups is confirmed, but in adults many cases occur without septicaemia. The mortality is currently very low.
Acute Disease↗
Respiratory sequelae and lung function after whooping cough in infancy.
The lung function of 31 children, aged 6-13 years, who had whooping cough as infants and 32 control children matched for age, sex, and residence area were compared in a community based cohort study. Family history of obstructive airway disease, smoking habits in the family, atopy, and other background factors examined were similar in the two groups. The ratios of recalled repeated acute respiratory infections did not differ among the groups. Children in the control group were slightly more involved in physical activities. History of obstructive airway disease, findings on chest radiography, and distribution of immunoglobulin concentrations, including IgE, did not differ significantly. Lung function before and after exercise and after inhalation of salbutamol were not different. No impairment of small airways was detected. Our data do not support the hypothesis that whooping cough in itself is a causal factor for later obstructive respiratory disease.
Adolescent↗
[Vaccines today and tomorrow. New vaccines against Haemophilus influenzae type b].
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Bacterial Vaccines↗
Concentrations of ceftazidime, tobramycin and ampicillin in the cerebrospinal fluid of newborn infants.
Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.
Ampicillin↗
Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate.
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Antibodies, Bacterial↗
Estimating incidence of whooping cough over time: a cross-sectional recall study of four Swedish birth cohorts.
Incidence of whooping cough was studied in Göteborg, Sweden, in four random samples of birth cohorts from 1972, 1977, 1978 and 1980. To obtain data a postal questionnaire to parents was used and methodologically explored. Vaccination data were taken from health cards. Four years after stopping vaccination cumulative incidence in the unvaccinated cohort born 1980 had risen to levels of the prevaccination era. Sex differences in susceptibility were not seen. Efficacy of the Swedish manufactured non-adsorbed whole cell pertussis vaccine was low. In a developed country like Sweden a cross-sectional study of random samples from the community with recall data may give useful information on the incidence of a disease like whooping cough at a comparatively low cost.
Cohort Studies↗
Etiology of community-acquired pneumonia in children based on antibody responses to bacterial and viral antigens.
The serologic responses to bacterial and viral antigens were determined in paired serum samples from 336 children, ages 1 month to 15 years, with roentgenographically verified community-acquired pneumonia. Significant increases in antibodies against one agent were found in 40% and against two or more agents in 8% of the children. There were significant increases in antibodies against respiratory syncytial virus in 20%, viruses of the influenza-parainfluenza group in 6% and adenovirus in 3%. A serologic response to one or more of the pneumococcal antigens used (type-specific capsular polysaccharide, C-polysaccharide and pneumolysin) was demonstrated in 13% of the patients. Ten percent of the children had significant increases in antibodies against Mycoplasma pneumoniae. Only three patients had increases against Haemophilus influenzae type b and one each against Legionella pneumophila and Chlamydia. Respiratory syncytial virus was the predominant etiologic agent in young children whereas M. pneumoniae was more frequent in the older age group.
Adenoviruses, Human↗
Subclass compositions of immunoglobulin G to pertussis toxin in patients with whooping cough, in healthy individuals, and in recipients of a pertussis toxoid vaccine.
The subclass composition of serum immunoglobulin G (IgG) antibodies against pertussis toxin was studied in 108 serum samples obtained during various stages of disease from 75 patients with whooping cough. IgG1 and IgG3 antibodies were detected in 92 and 42% of the samples, respectively, while only a few contained IgG2 or IgG4 antibodies. Similarly, IgG1 antibodies were predominant in serum samples from healthy children and adults, many of whom had a history of whooping cough several years earlier. Of 85 children and 30 adults with detectable levels of total IgG, 65 and 14 had IgG1 antibodies, respectively, while only 9 of them had IgG3 antibodies. Again, very few sera contained IgG2 or IgG4 antibodies. In contrast, 13 children vaccinated with an acellular aluminum-adsorbed pertussis toxoid vaccine responded mainly with IgG1 and IgG4 antibodies. In conclusion, this study showed that the subclass composition of IgG antibodies to pertussis toxin after natural infection consists mainly of IgG1 and to a certain extent of IgG3, while an aluminum-adsorbed pertussis toxoid induces IgG1 and IgG4 antibodies.
Adolescent↗
Comparison of serum concentrations of ceftazidime and tobramycin in newborn infants.
Peak and trough serum concentrations of ceftazidime and tobramycin were determined in neonates with suspected septicaemia in an open randomized study. Mean peak serum levels were 85 (+/- 4.4 SE) mg/l for ceftazidime and 5.8 (+/- 0.3 SE) mg/l for tobramycin. The peak serum levels of ceftazidime were well above the reported minimal inhibitory concentration (MIC)90 values of pathogenic bacteria encountered in neonates, while peak serum levels of tobramycin were lower than reported MIC90 values for Klebsiella, Pseudomonas, Enterobacter and Serratia species. Nine of 33 tobramycin-treated patients had potentially toxic trough serum levels (greater than 2 mg/l) and nine had subtherapeutic peak serum levels (less than 4 mg/l). The dosage of this antibiotic had to be changed frequently. In comparison only 2 of 29 ceftazidime-treated patients had subtherapeutic peak levels (less than 40 mg/l) and none had potentially toxic trough levels (greater than 40 mg/l). Ceftazidime, in comparison with tobramycin, has a more favourable antibacterial spectrum and routine determinations of peak and trough serum levels should not be necessary.
Ampicillin↗
Antibody response to pertussis toxin in patients with clinical pertussis measured by enzyme-linked immunosorbent assay.
Serum antibody response to pertussis toxin was measured by enzyme-linked immunosorbent assay in 172 patients with clinical symptoms typical of whooping cough. The diagnosis was verified by culture in 100 patients. Serum antibodies were either not detectable or present only at low levels in sera obtained in the early stage of disease. Significant changes in serum levels of IgG, IgM and/or IgA were demonstrated in 143 patients (83%). The lack of comparable increases in most of the other patients may be due to inappropriate timing of serum collection. Thus, detection of antibodies against pertussis toxin in paired serum samples can be used for serological diagnosis of pertussis. However, the presence of IgM and/or IgA in a single serum sample does not confirm a diagnosis of pertussis, since such antibodies were found in healthy adults as well as in patients two years after the disease. High levels of these antibodies are, however, suggestive of on-going or recent disease.
Adult↗
Serum antibody response to filamentous hemagglutinin in patients with clinical pertussis measured by an enzyme-linked immunosorbent assay.
Titers of antibodies to filamentous hemagglutinin (FHA) were determined by enzyme-linked immunosorbent assay in acute and convalescent phase serum samples from 158 patients with clinical symptoms typical of whooping-cough. In 96 of the patients the diagnosis was verified by culture. Significant changes in serum levels of IgG, IgM and/or IgA antibodies against FHA were demonstrated in 126 patients (80%). Thus, demonstration of significant changes in FHA antibody titers in serum can be used for serological diagnosis of pertussis. The results also show that high levels of IgG, IgM and/or IgA antibodies in a single serum sample suggest current pertussis infection, but if the diagnosis is based on determinations of FHA antibody titers in a single serum sample the sensitivity is low. The levels of antibody to FHA were compared with previously determined levels of antibodies to pertussis toxin. A significant antibody response against both FHA and pertussis toxin was seen in 111 patients (70%) while 147 patients (93%) developed a significant increase in antibodies against one or both antigens.
Adolescent↗
Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide.
A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.
Adolescent↗