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Biomedical subjects

M Granström

Publications and source records attributed to M Granström.

At least 73 records · Page 4Linked to original sources

Impact of pertussis on the afflicted child and family.

The effects of pertussis in an unimmunized population were investigated in 61 children consecutively identified by positive culture for Bordetella pertussis. Parents were interviewed twice, at a mean of 3 and 11 weeks after onset of symptoms. All children had a disease duration of more than 3 weeks. Behavioral changes were reported for 84% of the study children. Parents reported negative effects for themselves in 95% and for siblings in 63% of the families. The main problems were disturbance of night sleep, staying home from work and isolation of the family. Parental knowledge of the disease was generally good; a majority had few contacts with the medical services and coped with the disease themselves. Serious concerns for the child were reported by 51% of parents and fears for permanent sequelae by 10%. The attitude to pertussis vaccination was positive in 89% of cases at both interviews. The study has thus shown that pertussis in an unimmunized child population represents a heavy burden.

Child↗

Specific immunoglobulin for treatment of whooping cough.

Immunoglobulin treatment for whooping cough (pertussis) is widely believed to be ineffective although there are sound reasons for regarding the condition as a toxin-induced disease. We wondered whether the lack of success with pertussis immunoglobulins might be attributable to inadequate dose, so we designed a randomised, double-blind, placebo-controlled trial of two immunoglobulin preparations. The study was conducted at three Swedish hospitals. We enrolled 73 children aged less than 36 months who were admitted with a clinical diagnosis of whooping cough. On admission they were assigned to one of three groups: (a) monocomponent pertussis toxoid vaccine; (b) two-component acellular vaccine also containing filamentous haemagglutinin; or (c) 20% albumin solution (placebo). The immunoglobulins had a high antitoxin content and had been raised with acellular pertussis vaccines. Diagnosis of pertussis was confirmed by laboratory tests and the follow-up was completed in 67 children. The main study group consisted of 47 children with less than or equal to 14 days of disease before therapy. Duration of whoops post-treatment was 8.7 days (95% Cl 4.8, 12.6) in the 33 children receiving immunoglobulin vs 20.6 (95% Cl 11.9, 29.3) in the 14 receiving placebo (p = 0.0041). Mean number of whoops during the first week of follow-up was also significantly reduced (p = 0.0196). We found that early treatment was important, since the effect on duration of whoops was most pronounced when disease duration before treatment was less than or equal to 7 days. There were no significant differences between the two immunoglobulin preparations. High-dose specific pertussis immunoglobulin with a high antitoxin concentration has a beneficial effect in the treatment of whooping cough.

Child, Preschool↗

The melanophore aggregating response of isolated fish scales: a very rapid and sensitive diagnosis of whooping cough.

Pertussis toxin (PT) has been found to block noradrenaline-induced pigment aggregation in fish melanophores, and, based on this, a rapid and highly sensitive assay for PT was developed. Some preliminary results have also indicated that it may be possible to detect PT-like activity in saliva samples from patients with clinically suspected pertussis. In the present study the diagnostic value of the fish melanophore method was evaluated in 70 patients suspected of having pertussis; culture, serology and physician diagnosis were used as reference methods. In 60 of the patients, pertussis was verified by at least one of the reference methods. The melanophore test showed PT-like activity in saliva samples from 58 of the patients. Three patients with reference-verified pertussis showed no PT-like activity in the test; among these, one patient had been immunized and had also been treated with erythromycin during 3 days immediately prior to visiting the hospital. The melanophore test has three major advantages: it allows detection of pertussis in the early and curable stage of the disease; it takes only 2 h to perform; and it requires no sophisticated equipment.

Adolescent↗

Cumulative incidence of pertussis in an unvaccinated preschool cohort based on notifications, interview and serology.

The cumulative incidence of pertussis at six years of age in the first unvaccinated cohort after cessation of immunisation in Sweden was investigated by serological methods and by a validation of the national epidemiological surveillance system by reports from the Child Health Centres (CHCs). In 312/385 (81%) eligible children, both an interview with the parents and a blood sample from the child could be obtained. The CHC reports yielded a cumulative incidence of 31%, whereas the serological assays found 54%. Of the cases reported by the parents to the CHCs, 89% were seropositives. In the additional cases of pertussis reported at the study interview, only 61% could be confirmed (p less than 0.001). Among children with reported severe cough not suspected to be pertussis, 46% were seropositive, distributed as 33% seropositives in cases with cough duration of less than 4 weeks and 69% for longer coughs (p less than 0.01). In the CHC reports, the parental diagnosis was found to have been confirmed in three-quarters of cases by medical personnel. The CHC reporting system was thus found to be reliable with an observed specificity of 93%, but sensitivity of only 52%. Thus, even this surveillance system, which yields the highest incidence rates, underestimates the incidence of the disease.

Bordetella pertussis↗

Lipase versus teichoic acid and alpha-toxin as antigen in an enzyme immunoassay for serological diagnosis of Staphylococcus aureus infections.

Titres of IgG antibodies to Staphylococcus aureus lipase were analysed in 448 sera from patients suspected of having Staphylococcus aureus infections and the results compared to those for the routinely used staphylococcal antigens teichoic acid and alpha-toxin. The results indicated that determination of serum antibodies to lipase is a sensitive assay for serological diagnosis of staphylococcal infections and increased sensitivity may be achieved by selection of optimal antigen combinations.

Adolescent↗

Diagnostic value of clinical and bacteriological findings in pertussis.

Clinical and bacteriological findings in the diagnosis of pertussis were evaluated in 300 consecutive patients with parental or the patient's own suspicion of the disease. Serology was used as a reference method. Of the 285 (95%) patients fully sampled, 163 (57%) were diagnosed as having pertussis while the remaining 122 patients constituted the non-pertussis control group. The clinical and epidemiological data were collected at the first visit made on median day seven of illness. In this population of mainly unimmunised children, the highest predictive values were obtained for the physician's diagnosis of pertussis (100%) and for the physician's diagnosis of some other illness (93%). The only clinical symptom with a high predictive value for pertussis was the report of whoops (92%). Among epidemiological data the highest predictive value (90%) was obtained for reported household exposure in unimmunised children more than 1 year of age. Culture of Bordetella pertussis was found to have an overall 50% sensitivity. Isolation of other bacteria had no predictive value in the differential diagnosis of pertussis.

Adolescent↗

Bordetella pertussis adenylate cyclase activity in nasopharyngeal aspirates for rapid diagnosis of whooping cough in relation to culture and serology.

Adenylate cyclase activity, measured in 201 nasopharyngeal aspirates from patients presenting with own or parental suspicion of whooping cough, was compared to diagnosis made by culture and by serology in the culture negative cases. The median amount of cyclic AMP in samples from culture negative patients (n = 145) was 0.60 pmoles which differed significantly (p less than 0.001) from the median value 3.28 in samples from culture positive patients (n = 56). The median value 0.70 pmoles of cyclic AMP in samples from culture negative patients who were positive by serology (n = 54) did not differ significantly from the value of 0.57 pmoles in samples from serology negative patients (n = 91). With a limit for positive cyclic AMP set at 2 pmoles, 45 samples were positive. The sensitivity of the assay was 66% (37/56) in culture positive patients while the specificity was 93% (85/91) in the serology negative patients. The positive predictive value for the c-AMP test was 82% (37/45) in relation to culture and 87% (39/45) in relation to culture and/or serology. The results confirmed that measurement of adenylate cyclase activity in nasopharyngeal aspirates by an 1-h incubation method can serve as an early and rapid diagnostic method of pertussis infection. The low sensitivity of the c-AMP assay in samples from serology positive but culture negative patients indicates however, that this assay will have to be supplemented by serology for a high diagnostic sensitivity in all cases of pertussis.

Adenylyl Cyclases↗

Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis.

A sonicate antigen and two concentrations of a purified flagellum antigen of Borrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13% in the sonicate EIA to 31% in the best flagellum EIA assay (p = 0.01) in sera from patients with erythema migrans (n = 70), and from 34% to 55% (p = 0.01) in sera from patients with neuroborreliosis (n = 77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n = 20) was high in both assays: 90% in the sonicate EIA compared to 95% in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non-Borrelia etiology (n = 35), multiple sclerosis (n = 9) or syphilis (n = 24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p less than 0.01). It is concluded that purified Borrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis.

Acrodermatitis↗

DNA hybridization for diagnosis of pertussis.

The aim of the present study was to evaluate a mixed phase DNA hybridization assay for detection of Bordetella pertussis and Bordetella parapertussis in nasopharyngeal aspirates from patients with suspected pertussis. Among 179 consecutive patients with own or parental suspicion of pertussis, the diagnosis was confirmed in 103 patients by serology and in 52/103 (50%) cases also by culture. The remaining 76 patients served as nonpertussis controls. Direct hybridization was positive in 38% samples with serology as reference method, a non-significant difference to the 50% sensitivity for culture. Preculture of samples on membranes for 24, 48 and 72 h gave a significantly higher sensitivity only with 72 h preculture, 69% vs 50% (P = 0.007). The 72h preculture gave, however, also a significant decrease of specificity, 87% vs 100% for routine culture (P = 0.001) and is not a more rapid diagnostic method. The result shows that rapid diagnosis by DNA hybridization can be achieved in a large proportion of pertussis cases. The presence of smaller numbers of bacteria in samples only positive after preculture indicate that DNA hybridization could be a highly sensitive diagnostic method with further development of more rapid amplification systems.

Bordetella↗

Long term serologic follow-up after pertussis immunization.

Neutralizing antibodies to pertussis toxin (antitoxin) were determined in 201 blood samples from 4-year-old children. They had received primary immunization at 6 to 8 months of age with an acellular (n = 149) or a whole cell (n = 52) pertussis vaccine and 195 of them had received a booster dose of the acellular vaccine 9 to 16 months later. Data on exposure to pertussis and occurrence of pertussis were also collected. There was a rapid decrease of antitoxin between immediate postbooster titers and those measured 24 months later. This decrease per month was significantly greater than that after the primary immunization series (P less than 0.001). Neither the number nor the spacing of acellular vaccine doses given for primary series influenced the titers found 24 months after the booster. An antitoxin response was still measurable in 86% of the 196 four-year-old children. None of 19 exposed children developed whooping cough, which suggested that the antibody concentrations during the follow-up period were sufficient for protection. The results indicate a need for long term follow-up studies in the evaluation of new vaccines and immunization schedules.

Antibodies, Bacterial↗

Increased dosage of diphtheria toxoid for basic immunization of adults.

Basic immunization of adults with increased dosages of a diphtheria toxoid vaccine (2100 flocculation units (Lf)/mg) was evaluated. Three injections of 7.5 Lf or 15 Lf diphtheria toxoid were given to 243 adults who had a history of no more than one previous vaccine injection. Systemic reactions were rare in both groups. Following the first two injections, local reactions (greater than 5 cm) were observed in 6-14% of the adults. After the third injection, 35% of adults in the 15 Lf group reported a local reaction (greater than 5 cm) compared to 11% in the 7.5 Lf group (p less than 0.001). The 15 Lf dose elicited a better antitoxin response than the 7.5 Lf dose. In a seronegative subgroup including 65 vaccinees who showed no booster response to the first vaccination, 79% had a postvaccination titer of greater than or equal to 0.1 IU/ml and 28% a titer of greater than or equal to IU/ml after the third injection of 7.5 Lf. The corresponding numbers in the 15 Lf group were 94% and 44%, respectively. The study demonstrates that 7.5 Lf and 15 Lf diphtheria toxoid of high purity can safely be given to adults for basic immunization. The higher dose is more immunogenic but local reactions increase after the third injection.

Adult↗

Immunity and immunization of children against diphtheria in Sweden.

The level of immunity to diphtheria and the effect of vaccination with different doses of diphtheria toxoid was investigated. The 457 study children, 6, 10 and 16 years of age, had as infants received routine primary vaccination with three doses of diphtheria-tetanus-toxoid or diphtheria-tetanus-pertussis vaccine, and the 16 year-olds also had received a booster dose of tetanus with a small dose of diphtheria at the age of ten. Prior to the study booster, 15% of the 6-year-olds had antitoxin levels against diphtheria less than 0.01 IU/ml, the given minimum level for protection. Of the 10-year-olds, 48% had titres less than 0.01 IU/ml, while the corresponding figure for the 16-year-olds was 24%. After a booster injection of 0.1, 0.25 or 0.5 ml of diphtheria-tetanus vaccine, more than 97% of the children showed titre levels greater than or equal to 0.1 IU/ml, while levels of greater than or equal to 1 IU/ml, indicating titres sufficient for long-term protection, were attained by 23-96%. Systemic reactions were few and moderate. Local reactions were of little clinical significance. In a group of 5-years-olds given diphtheria-tetanus primary vaccinations over wider intervals, only 1.4% had antitoxin titres less than 0.01 IU/ml. The results show a need for serologic monitoring of vaccination programmes.

Adolescent↗

Adverse reactions and antibody response to an acellular pertussis toxoid vaccine in adult volunteers.

A monovalent pertussis toxoid vaccine (JNIH-7, Biken, Japan) was evaluated for reactogenicity and immunogenicity in 20 healthy adults (phase 1 study). Fever of greater than or equal to 38 degrees C was recorded in 2/20; local reactions started in 2/20 on day 1 (early onset) and in 3/20 on day 7 (late onset). All 15/15 subjects tested showed a significant antibody response to pertussis toxin by neutralization or enzyme-linked immunosorbent assay. Significantly elevated antibodies were still detected in 12/13 subjects 32 months after the single subcutaneous dose of vaccine.

Adult↗

Sixteen-month follow-up of antibodies to pertussis toxin after primary immunization with acellular or whole cell vaccine.

Antibodies to pertussis toxin (antitoxin) were measured in three blood samples drawn during a 16- to 17-month follow-up of infants immunized with adsorbed two component acellular pertussis vaccine (JNIH-6) or plain whole cell vaccine. A significant decrease of antitoxin concentration was noted between each follow-up in the acellular vaccine groups (P less than 0.005). The higher antitoxin titers induced by three doses or by two doses spaced by 2 months compared with two doses with 1-month interval disappeared with time. The antitoxin titers among high responders to three doses of whole cell vaccine paralleled those of the acellular vaccinees but at a significantly lower level. Reported exposure to pertussis did not significantly alter the decrease of antitoxin titers. The study also showed that acellular pertussis vaccine induced an antitoxin response still measurable in greater than or equal to 97 and greater than or equal to 91% of samples drawn 10 to 11 and 16 to 17 months after primary immunization, respectively.

Antitoxins↗

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↗

Immunoglobulin E response to pertussis toxin in whooping cough and after immunization with a whole-cell and an acellular pertussis vaccine.

Immunoglobulin E antibodies to pertussis toxin (PT-IgE) were demonstrated in 15 of 23 (65%) patients with culture-confirmed pertussis. In 6 individuals there was a low-grade PT-IgE response after 6-9 weeks of disease and in 9 a rapid PT-IgE response, appearing 1-3 weeks after onset of symptoms. The PT-IgE antibody levels in immunized individuals were higher than in the non immunized. Following primary immunization of 23 children with a monovalent whole-cell pertussis vaccine (Burroughs-Wellcome, UK) or with an acellular pertussis vaccine (JNIH-6, Biken, Japan) a late low-grade PT-IgE response was found in 8 (35%). In 7/10 children previously immunized with the JNIH-6, a booster injection 16 months later with the same vaccine resulted in a rapidly appearing PT-IgE antibody response. In contrast, none of 13 children initially immunized with the monovalent whole-cell vaccine and then boostered with either this vaccine or JNIH-6 had detectable PT-IgE antibodies after the booster injection. The study shows that IgE-antibodies to pertussis toxin commonly appear in patients with whooping cough and that the kinetics and the magnitude of the response is influenced by previous exposure to the antigen. A PT-IgE response may also follow pertussis immunization.

Antibodies, Bacterial↗

Immune status and booster effects of low doses of diphtheria toxoid in Swedish medical personnel.

During a diphtheria outbreak among Swedish alcoholics in 1984-1985, only 60% of 328 medical staff at risk for exposure had diphtheria antitoxin titers greater than or equal to 0.01 IU/ml, which is usually considered to give relative protection. 21% had levels between 0.01-0.09 IU/ml and the remaining 39% had titers greater than or equal to 0.1 IU/ml. Booster doses of 0.5 Lf-12.5 Lf of diphtheria toxoid were given to 450 vaccinees. Of 72 individuals with low pre-immunization titers, who were immunized with less than or equal to 2.5 Lf diphtheria toxoid, 40% failed to reach greater than or equal to 0.1 IU/ml when analyzed 4 weeks after vaccination. Local tenderness and swelling greater than 5 cm at the site of injection or general discomfort was found in 11% of those immunized with low dose diphtheria toxoid (less than or equal to 2.5 Lf). When the dose 0.5 Lf of diphtheria toxoid was combined with tetanus toxoid (3.75 Lf) the frequency of adverse reactions increased to 34% (p less than 0.001). The study shows that vaccination status in medical personnel must also be continuously examined in countries where diphtheria is rare and that low booster doses of diphtheria toxoid may not achieve an adequate immune response.

Adolescent↗