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Biomedical subjects

M Granström

Publications and source records attributed to M Granström.

At least 91 records · Page 5Linked to original sources

Adverse reactions and serologic response to a booster dose of acellular pertussis vaccine in children immunized with acellular or whole-cell vaccine as infants.

Adverse reactions and antibody response to pertussis toxin, ie, antitoxin, after a booster injection of an acellular pertussis vaccine were studied in 2-year-old children. A majority (212/241) of the children had previously been immunized with either two or three doses of the acellular vaccine at the ages of 6, 7, and 8 months. The other 29/241 children had received three doses of a plain whole-cell pertussis vaccine at the same ages. In the children who received primary immunization with the acellular vaccine, two cases of more serious systemic reactions occurred in close temporal association with the booster injection. Less serious systemic reactions were few. Local reactions were more common in the children only immunized with the acellular vaccine. Large reactions (greater than 10 cm) were only seen in this group. A good antitoxin response was elicited in both groups. The geometric mean titer in the former whole-cell vaccine recipients was significantly higher than in the children who received only acellular vaccine. The study raised some questions concerning differences in reactogenicity and immune response after a booster injection of an acellular vaccine depending on the type of pertussis vaccine given to infants for the primary immunization.

Antibodies, Bacterial↗

Protective efficacy of a whole cell pertussis vaccine.

A trial of the efficacy of a plain whole cell pertussis vaccine was conducted in Sweden. In this non-blinded trial 525 infants aged 2 months who were born on days with an even number received three doses of vaccine one month apart and 615 infants of the same age who were born on days with an odd number were enrolled as controls. During the 18 months of follow up there were 55 cases of pertussis. The attack rate was 1.5% (8/525) among the vaccinated children and 7.6% (47/615) among the unvaccinated children (p less than 0.001). The estimated efficacy of the vaccine was 80% (95% confidence interval 58 to 90). The estimated efficacy of pertussis vaccine was similar to that observed in British trials over 30 years ago.

Clinical Trials as Topic↗

Protective effect of acellular pertussis vaccines.

Two acellular pertussis vaccines, a mono-component toxoid of pertussis toxin and a two-component vaccine containing both the toxoid and filamentous haemagglutinin, were used for primary immunization of infants 5 1/2 to 10 months of age in two clinical trials in Sweden. Over a follow-up period of 12 to 17 months, 37 children were exposed to pertussis in the household or a daycare centre. Only one child developed mild, culture-confirmed pertussis as opposed to the expected number of 30 to 33 cases based on an assumed attack rate of 80-90% in non-immunized children. These preliminary findings indicate that, given as primary immunization to infants, the vaccines provide protection against pertussis.

Antitoxins↗

Serum antibodies to pneumolysin in patients with pneumonia.

Serum antibodies to purified pneumolysin were determined by enzyme-linked immunosorbent assay (ELISA) in paired samples from 406 adult patients with community-acquired pneumonia and in samples from 184 healthy controls. A high sensitivity (83%) was obtained in patients with blood culture-confirmed pneumococcal pneumonia. In patients with a tentative pneumococcal diagnosis based on culture of samples from the sputum or the nasopharynx, 45% were positive by ELISA. The difference likely reflected the different relevance of cultural findings for the diagnosis of pneumococcal pneumonia. A significant rise in ELISA titer was found in 17% of the patients. When the diagnosis was also based on high titers, 25% were positive. Pneumococcal pneumonia diagnosed by the pneumolysin ELISA was significantly more common in the patients with a more severe disease and who required hospitalization (21 versus 5% for outpatients). Younger patients were more often positive for pneumococci as determined by high titers, while older patients showed titer rises. Mixed infections with other infectious agents were not uncommon. The finding of low titers in acute-phase samples from positive patients and in the youngest and oldest age groups of healthy controls were unexpected, indicating that further studies on the role of pneumolysin in pneumococcal disease are warranted.

Adolescent↗

Enzyme-linked immunosorbent assay to evaluate the immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans.

A highly sensitive enzyme-linked immunosorbent assay was developed for Klebsiella capsular polysaccharide (CPS) and used to evaluate the immunoglobulin G (IgG) antibody response to a 24-valent CPS vaccine in seven adult volunteers. The median rise in titer to all vaccine antigens in samples from the volunteers was significant (twofold or greater). Significant IgG responses to 11 immunologically related serotypes not included in the vaccine were also noted. The mean cross-reacting IgG titer of 127.2 was only slightly lower than the mean titer of 175.7 to the serotypes in the vaccine (P less than 0.05). The mean 29.9-fold increase in titer to the serotypes in the vaccine was significantly higher than the mean 13.5-fold increase in titer to the additional antigens (P less than 0.001). The difference was partly because of the significantly lower (P less than 0.01) natural antibody titers in the preimmune sera to the serotypes in the vaccine, compared with those to serotypes not included in the vaccine. The selection of vaccine serotypes was based on the frequency of serotype isolation from cases of Klebsiella bacteremia. The above findings, which show low levels of natural antibody to these serotypes, support the hypothesis that anti-CPS antibody is protective against bacteremic disease.

Antibody Formation↗

Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough.

Specific immunoglobulin A (IgA) to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) was determined in mucosal secretions by an enzyme-linked immunosorbent assay (ELISA). It took 3 to 4 h to complete the ELISA. The upper limits of normal values for age were determined in nasopharyngeal (NPH) secretions from 23 patients with viral infections and in 10 healthy adults working with pertussis patients or cultures. A significant IgA response to FHA was found in 38 of 54 (70%) and to PT in 28 of 54 (52%) NPH secretions from patients with pertussis confirmed by culture, serology, or both. The rate of positive responses to either antigen (44 of 54 [81%]) was significantly higher than that by culture alone (29 of 54 [54%]; P less than 0.01). The rate of positive responses increased from 65% in patients with symptoms for 1 week or less to 87 to 92% in patients with symptoms for 2 or more weeks. The specific IgA response to PT was found in 100% of NPH samples from 17 unimmunized children less than 3 years of age and in only 30% of adults and immunized children greater than 3 years of age. A response to FHA was found in 65 to 73% of the NPH secretions in all age groups. Saliva samples were found to contain specific IgA to FHA and PT in all age groups, but these were of diagnostic value in 50% (11 of 22) of the adult patients. The specificity of the ELISA was 100% (10 of 10 negatives) in NPH secretions from patients with pertussis-like cough who had negative cultures and serology. The results indicate that determination of specific IgA to PT and FHA in NPH aspirates represents a sensitive and rapid diagnostic method for the detection of pertussis.

Adolescent↗

Evaluation of serologic assays for diagnosis of whooping cough.

An enzyme-linked immunosorbent assay (ELISA) for the immunoglobulin G (IgG), IgM, and IgA response to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) and a neutralization test (NT) in a microplate tissue culture assay for neutralizing antibodies to PT were evaluated in paired sera from 90 patients with culture-confirmed pertussis. Eighty patients were children (age, less than 15 years), and 6 of 80 children had been immunized with three doses of diphtheria-tetanus-pertussis vaccine as infants. A significant titer rise (greater than or equal to twofold), determined by ELISA, of IgG, IgM, and IgA to FHA was recorded in 75 (83%), 28 (31%), and 47 (52%) of the patients, respectively. A significant titer rise to PT in IgG was found in 83 (92%), IgM in 29 (32%), and IgA in 44 (49%) of the patients. A significant titer rise to FHA or PT in IgG was found in 88 (98%) of the patients, in combination with a significant rise in the titer of IgA to FHA. These data were obtained in a single serum dilution of 1:500. Titrations performed later showed that the titer rise to FHA in IgG was a mean of 6.5-fold, which was significantly lower than the mean 67.0-fold rise in IgG to PT (P less than 0.001). The mean titer of IgG to FHA in convalescent-phase serum was 270, which was also significantly lower than the mean PT titer of 2,943 (P less than 0.001). A significant rise (greater than or equal to fourfold) in PT titer by NT was found in 58 of 83 (70%) of the patients. The NT was significantly less sensitive than the ELISA for the determination of the IgG titer to PT ( P< 0.001). Results showed that a 100% (90 of 90) sensitivity in terms of titer rises was achieved in the serologic diagnosis of pertussis by ELISA in a single-point determination of the IgG and IgA responses to FHA and of the IgG response to PT.

Adolescent↗

Management of pregnant women with contagious infections at delivery.

Since 1970 pregnant women with contagious infections in the country of Stockholm have been delivered at the Danderyd Hospital, the only hospital in the area which has departments of obstetrics and pediatrics as well as infectious diseases. This paper presents data from a prospective study carried out during a period of 10 years (1975-1984). The study includes 303 women and their newborns who for various reasons were transferred to the Department of Infectious Diseases (DID) before or after delivery. A comprehensive microbiological investigation was made in order to establish an etiological diagnosis in all women included in the study. A possible transmission of the infection from the mother to her fetus/child before or after delivery was also investigated. Only 0.17% of the pregnant women in the area needed care at the DID at delivery or in the puerperal period. 9% of the deliveries occurred at another hospital, 32% at the DID and the remaining at the obstetrical department, Danderyd Hospital. The rate of complications, including cesarean sections, was 12%. Of the 165 women suffering from an infectious disease at the time of delivery, 40% had a verified viral disease--in most cases varicella or mumps, 28% had a bacterial infection and for 32% no etiology of the disease could be established. The study population also includes women suspected either to be incubated with a contagious disease or to be carriers of infectious agents, as well as healthy mothers whose newborns were expected to be carriers of infectious agents such as rubella and varicella. None of the women died during the study period but 5 were seriously ill and 3 needed intensive care. The rate of stillbirths was the same as reported among all births in the country of Stockholm but the perinatal mortality rate was significantly higher (see also a following article, ref. 27). Our routines prove the necessity to take special care of pregnant women carrying a contagious infectious agent at term.

Communicable Disease Control↗

A longterm follow-up study of children born to women with contagious diseases at delivery.

Data are presented from a long-term follow-up study of 308 live born children to women admitted post partum to the Department of Infectious Diseases (DID), Danderyd Hospital, Sweden, during a 10-year period (1975-1984) for avoiding nosocomial transmission of infections in the obstetrical wards. The rate of stillbirths (1/309 deliveries) was not higher than reported for all births in Stockholm. 20% of the live born children were transferred within 24 h after birth to the pediatric department for observation, but half of them could return to their mothers at the DID within 6 days (generally 3 days). Four newborns were treated at an intensive care unit. Only 3 fatalities occurred, all of them among newborns to mothers with an overt infection at delivery. The fatality rate (1.8%) was significantly higher among the newborns of these mothers than normally (0.3%) noted among all children born in Stockholm county during the period studied. Two of the 3 newborns, who all died within 3 days of life, had a low birth weight (600 and 1,000 g). The total number of newborns with low birth weights (less than 2,500 g) was, however, not higher in the above-mentioned group of newborns than for all children born in Stockholm county 1980. None of the 3 fatalities was caused by infection transmitted from the mother. No further deaths occurred. Infections in pregnancy at term, at birth or post partum were transmitted from the women to 41 (13%) of their newborns.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Primary immunization of infants with an acellular pertussis vaccine in a double-blind randomized clinical trial.

The rate of adverse reactions and the immunogenicity of a two-component acellular pertussis vaccine as compared with a plain whole-cell vaccine and a placebo were evaluated for primary immunization in 319 6-month-old infants in a double-blind randomized clinical trial. The acellular vaccine produced few and mild systemic and local reactions. Fever (greater than or equal to 38 degrees C) occurred in 6% to 8% of acellular vaccinees as opposed to 25% to 37% of whole-cell vaccinees. Redness (greater than or equal to 1 cm) appeared in 2% to 13% of the acellular vaccine and 24% to 32% of the whole-cell vaccine recipients. Antibody response to pertussis toxin measured in a neutralization test was obtained in 97% to 100% of the infants receiving either two or three doses of the acellular vaccine as compared to 59% after three doses of whole-cell vaccine.

Antitoxins↗

A clinical trial of a monocomponent pertussis toxoid vaccine.

We compared a monocomponent pertussis toxoid vaccine preparation (JNIH-7) in a double-blind, randomized study with another component vaccine (JNIH-6) containing pertussis toxoid and filamentous hemagglutinin in equal proportions. Monocomponent pertussis toxoid vaccines have not been tested previously in children. This trial comprised 255 previously nonimmunized children 6 to 10 months old who were given two 0.5-mL subcutaneous injections of either vaccine four to five weeks apart. Prevaccination and postvaccination serum samples from 235 infants showed an antitoxin seroconversion rate of 100% in both groups. Adverse reactions were few and mild, with local reactions occurring more often after administration of the second dose and among recipients of the two-component vaccine (P less than .05).

Antibody Formation↗

Adverse reactions and immunogenicity in adults to regular and increased dosage of diphtheria vaccine.

Booster doses of 3 Lf or 7.5 Lf of a regular diphtheria vaccine were given to 200 previously immunized adult volunteers. The toxoid was prepared from toxin with a purity of 2100 Lf/mg protein nitrogen and adsorbed to aluminium phosphate. Systemic reactions were rare and no severe symptoms were observed. Local reactions occurred in 40-50% of the vaccinees, but in only 7.5% were they of clinical significance, i.e. an area of redness/swelling greater than 5 cm. The two doses did not cause significant differences in reaction rates, and the 7.5 Lf dose elicited a better antitoxin response. Thus, a dose of 7.5 Lf diphtheria toxoid of similar purity can safely be given to adults in vaccines.

Adult↗

Acellular pertussis vaccine in adults: adverse reactions and immune response.

An acellular pertussis vaccine JNIH-6 containing pertussis toxin and filamentous hemagglutinin was evaluated in adult volunteers with regard to adverse reactions and antibody response. Adverse reactions were few and mild. A late onset local reaction was seen in 22 of the 47 vaccinees (47%) as compared to none of the 20 subjects receiving a placebo, the carrier solution of aluminium phosphate of the vaccine. The reaction, which manifested itself on the 6th to 8th day after vaccination, consisted in all cases of an induration and/or swelling considered insignificant by the majority of the subjects. The reaction was only found in vaccinees receiving a first dose of vaccine and was independent of the prevaccination antitoxin level. The vaccine induced a highly satisfactory antibody response to both filamentous hemagglutinin and pertussis toxin.

Adult↗

A sandwich ELISA for bovine serum in viral vaccines.

A double antibody sandwich ELISA for the detection of bovine serum in viral vaccines was developed and standardized with commercially available reagents. The detection limit by ELISA was 0.5 ng ml-1. ELISA was found to be 50-400 times more sensitive than the currently used assays. It was concluded that ELISA is a specific, sensitive and reproducible method for the determination of residual amounts of bovine serum in viral vaccines.

Animals↗

Serological diagnosis of Borrelia meningitis.

The antibody response against a Borrelia strain isolated from Swedish Ixodes ricinus ticks was determined by enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) of cerebrospinal fluid (CSF) and serum specimens from 45 patients with chronic meningitis. Probable Borrelia etiology could be demonstrated in 41 of 45 (91%) patients with clinical symptoms of chronic meningitis. Approximately 25% of the patients had significantly elevated titer of antibody to the spirochete in CSF but not in serum. Patients with short duration of disease were especially prone to be antibody negative in serum but positive in CSF. Significant rise in serum antibody titers was seldom demonstrated in patients treated with antibiotics.

Animals↗

Use of erythromycin to prevent pertussis in newborns of mothers with pertussis.

During the period 1975-1985, 35 women with serology- or culture-confirmed pertussis at the time of labor were admitted to the Danderyd Hospital (Danderyd, Sweden). In 32 cases, the mothers were allowed to nurse their newborns while receiving erythromycin therapy. Erythromycin prophylaxis was given to 28 newborns. None of the newborns developed clinical or laboratory signs of whooping cough. The therapy was well tolerated by the newborns and did not affect the microflora in the gut. Maternal antibodies to pertussis toxin and to the filamentous hemagglutinin were found in cord blood, and levels decreased during the follow-up period. The study demonstrated that mothers with pertussis can safely be allowed to nurse their infants if both receive erythromycin.

Antibodies, Bacterial↗

Immunological relation between serum antibodies against pneumolysin and against streptolysin O.

The immunological relation between serum antibodies to pneumolysin and to streptolysin O was studied in patients with pneumococcal pneumonia (n = 40), patients with infections due to beta-haemolytic streptococci (n = 35), healthy human controls (n = 60) and in rabbits immunized with pneumolysin. There was no correlation between anti-pneumolysin and anti-streptolysin O titers (r = -0.279). The distribution of anti-pneumolysin titers in patients with high anti-streptolysin O titers did not differ from healthy controls. However, there was a tendency to increased or rising anti-streptolysin O titers in patients with pneumococcal infection. Antibodies obtained during pneumococcal infection might thus give false-positive reactions in the streptolysin O neutralization test. Serum antibodies to streptolysin O do not cross-react with pneumolysin in an ELISA. The pneumolysin ELISA for detection of pneumococcal disease will therefore not be disturbed by false-positive reactions due to antibodies directed against beta-haemolytic streptococci.

Animals↗

Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis.

Serum immunoglobulin G to four purified antigens from Pseudomonas aeruginosa, phospholipase C, alkaline protease, exotoxin A, and elastase, were determined in 62 patients with cystic fibrosis by enzyme-linked immunosorbent assay. The patients were followed for 12 to 24 months in a prospective study. Increased titers, i.e., titers more than 2 standard deviations above those of normal controls, were exclusively found in patients chronically colonized with P. aeruginosa and not in patients harboring only Staphylococcus aureus. The frequencies of elevated titers of antibody to the different antigens varied from 100% (phospholipase C) to 58% (alkaline protease and exotoxin A) to 15% (elastase) in the chronically colonized patients. Mean serum titer levels, expressed as multiples of the age-correlated upper normal limit (=1), were significantly higher to phospholipase C in patients with dual colonization with P. aeruginosa and S. aureus than in those colonized only with P. aeruginosa (P less than 0.001). Conversely, the other three antigens showed significantly higher serum antibody titer levels in patients harboring only P. aeruginosa (P less than 0.001). In five patients who became colonized with P. aeruginosa during the study period, serum antibodies to phospholipase C and exotoxin A increased first. Exceptions to the general pattern of antibody responses were found in three patients chronically colonized with Escherichia coli. They showed a delayed enhancement of anti-phospholipase C titers after the chronic P. aeruginosa colonization. Serum titers were not influenced by exacerbations of pulmonary infection or by antimicrobial therapy. The determination of titers of serum antibody to phospholipase C seems to be a valuable indicator of a chronic colonization with P. aeruginosa. The results further suggest that bacterial metabolism and interactions may influence the antibody response.

ADP Ribose Transferases↗