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Biomedical subjects

H Fredlund

Publications and source records attributed to H Fredlund.

54 records · Page 3Linked to original sources

The impact of Haemophilus influenzae type b vaccination in Sweden.

The number of patients with meningitis and bacteremia due to Haemophilus influenzae was studied in Sweden over the period 1987-1994. Conjugated H. influenzae type b vaccines were introduced in Sweden in 1992, and all children born after December 31, 1992, were offered vaccination free of charge. A rapid decline of H. influenzae meningitis and bacteraemia was observed in the autumn of 1993, when the expected peak incidence failed to appear. In the prevaccination period 1987-1991, the average annual incidence (cases/100,000) was 34.4 in children aged 0-4 years. In 1994, the annual incidence fell to 3.5. No significant decline was observed in older children or adults. There was a 92% reduction in the number of meningitis cases and an 83% reduction in cases of bacteraemia. A similar decline was noted in 2 regions which followed different strategies for the introduction of the vaccination programme.

Adult↗

Different seroprevalences of antibodies against Neisseria meningitidis serogroup A and Haemophilus influenzae type b in Sudanese and Swedish children.

Sampling of sera from 202 Sudanese and 124 Swedish children 1-14 years of age was conducted at the end of the 1980s presenting an opportunity to compare the seroprevalence of anti-Neisseria meningitidis (MC) serogroup A antibodies in an area immediately before outbreak of an epidemic (Sudan 1988) with a low endemic area (Sweden). An ELISA antibody assay was developed for detection of antibodies against capsular polysaccharide of MC serogroup A and Haemophilus influenzae type b (Hib). Serum antibody against MC serogroup A was found significantly more frequently in Sudanese than in Swedish children. This indicates that factors other than herd immunity, as measured by serum antibodies against MC serogroup A polysaccharide, are important for avoidance of an MC serogroup A epidemic. The seroprevalence of Hib antibodies was, in contrast, significantly higher in Swedish than in Sudanese children, especially for 5-9-year-old children. A possible explanation may be the different systems of day-care of children in the two countries.

Adolescent↗

Incidence of Helicobacter pylori strains activating neutrophils in patients with peptic ulcer disease.

A total of 61 human gastric isolates of Helicobacter pylori were studied for their ability to induce an oxidative burst in human neutrophils measured by luminol enhanced chemiluminescence. About one third of the strains induced strong and rapid chemiluminescence in neutrophils even without serum opsonins and agglutinated these cells on glass slides within two minutes. For other strains complement was required, although even then the reactions remained at a lower level. The activating and agglutinating property was bound to the cells, heat labile, and sensitive to several enzymes but resistant to acid. Strains possessing such activity were more common in patients with peptic ulcer disease than in patients with active chronic gastritis only (p = 0.0261, Fisher's exact test, two tailed). The activity shown might be a new indicator for ulcerogenic strains and could also partly explain the accumulation of neutrophils in the gastric mucosa during H pylori infection.

Agglutination↗

Serum bactericidal activity and induction of chemiluminescence of polymorphonuclear leukocytes: complement activation pathway requirements in defense against Neisseria meningitidis.

Serum bactericidal activity and chemiluminescence (CL) responses of polymorphonuclear leukocytes (PMNL) to pathogenic Neisseria meningitidis serogroups B and W-135 and to nonpathogenic serogroup 29E were examined with pooled normal human serum depleted of the complement proteins C1q, factor D, properdin and C5. Purified C1q, factor D, properdin and C5 were added alone or in combination. For investigation of serogroup W-135 meningococci, a C1q, factor D and properdin-depleted postvaccination serum with high concentrations of anticapsular antibodies was also used. Serogroup B and W-135 cultured to log phase were resistant to the bactericidal activity of pooled normal human serum but were efficiently killed through the classical pathway alone when the bacteria were cultured to stationary phase. Nonpathogenic serogroup 29E meningococci in log or stationary growth phases were efficiently killed in serum, predominantly through the classical pathway. Serogroup W-135 meningococci grown to log phase were resistant to classical pathway-mediated bactericidal activity in postvaccination serum but were killed on addition of alternative pathway proteins. Stationary phase serogroup W-135 meningococci were killed through both pathways in the postvaccination serum. In the pooled normal human serum CL responses of PMNL were consistently more pronounced with fully reconstituted C1q, factor D, properdin, C5-depleted serum than with serum reconstituted with C1q, factor D and properdin suggesting contribution of actions related to terminal components. In the absence of C1q, serogroup W-135 meningococci in postvaccination serum induced a significant but delayed alternative pathway-mediated CL response. CL responses induced by serum-opsonized meningococci, in contrast to serum bactericidal activity, were not influenced by culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Bactericidal Activity↗

Serum factors and polymorphonuclear leukocytes in human host defence against Neisseria meningitidis. Studies of interactions with special reference to a chemiluminometric technique.

Luminol enhanced chemiluminescence (CL) was used to study the interactions of various serogroups of opsonized or nonopsonized meningococci (MC) with polymorphonuclear leukocytes (PMNL), and the results were compared with those of functional (serum bactericidal activity = SBA, phagocytic killing = PK) and nonfunctional (EIA and IFL) antibody tests. The inherent problems of inter-assay and day-to-day variations of the CL technique were solved by indexing the responses with the use of an international serogroup X reference MC strain (NCTC 10790). When opsonized with serum from healthy adults without a history of meningococcal (MC) disease, the pathogenic MC strains of serogroups A, B, C, Y (Orebro variant) and W-135 gave significantly lower CL indexes than the apathogenic ones of serogroups Y, Z, and 29E and of nongroupable strains (p < 0.001). The same patterns were obtained when the strains were opsonized with serum from Swedish children 1-3 years old and also with serum A Sudanese children. Higher levels of antibodies against MC serogroup A polysaccharide were found in sera from Sudanese children than in those of Swedish ones. Correspondingly, the CL indexes for MC of serogroup A were somewhat higher for the Sudanese children than for the Swedish ones. In spite of this an MC epidemic due to a serogroup A strain could not be avoided in Sudan, but could in Sweden, where the same strain was introduced, indicating that other factors than serum immunity are of importance for avoidance of an MC serogroup A epidemic. In various series of experiments it was shown that the CL technique, like the SBA and PK tests, can discriminate between functional and nonfunctional antibodies in healthy individuals, in patients during and after MC disease and before and after vaccination, whereas EIA and IFL tests cannot. It was also shown that in the presence of serum from healthy individuals without a history of MC disease, both the classical and alternative complement pathways are activated to kill or to induce phagocytosis of apathogenic MC, whereas only the classical pathway is activated for the pathogenic ones. In the presence of serum from an individual vaccinated with MC capsular polysaccharide vaccine (high levels of anti-MC capsular polysaccharide antibodies), the pathogenic MC activate both the classical and alternative complement pathways for induction of phagocytosis. It is concluded that the standardized CL indexing technique for pathogenic and apathogenic MC has several advantages over the laborious and cumbersome SBA and PK assays in demonstrating and measuring the presence of functional anti-MC antibodies. It also has the capacity to discriminate pathogenic from apathogenic MC, and under certain circumstances it might be used as a diagnostic tool.

Adolescent↗

Early development in healthy children of serum opsonins against nonpathogenic Neisseria meningitidis.

In an earlier study, with the use of chemiluminescence (CL) and phagocytic killing, we could show that in the presence of serum from healthy adults polymorphonuclear leukocytes (PMNL) efficiently handle nonpathogenic Neisseria meningitidis strains, in sharp contrast to those associated with clinical disease. The major part of this difference was dependent on serum factors. In the present study 84 serum samples from children 1-3, 4-6, 7-9, and 10-14 years old were studied by the CL technique according to their ability to opsonize meningococci. There was a highly significant difference (p less than 0.001) in all four age groups when the CL indexes obtained with the pathogenic meningococci of the serogroups A, B and C were compared with those of the nonpathogenic menigococci: serogroup 29E and nongroupable meningococci. These findings imply that the ability to opsonize so-called nonpathogenic meningococci is developed early in life and may explain why they are only occasionally able to cause disease.

Adolescent↗

Mobiluncus species in bacterial vaginosis: aspects of pathogenesis.

Mobiluncus is an anaerobic motile rod associated with bacterial vaginosis. In this work, luminol-enhanced chemiluminescence was used to study the ability of Mobiluncus spp. from the vaginas of women with bacterial vaginosis to induce, in the presence of normal adult serum, oxidative metabolism of polymorphonuclear leukocytes, which is an indirect measure of phagocytic activity. M. curtisii induced a significantly (p less than 0.05) lower response than M. mulieris, which indicates that M. curtisii escapes phagocytosis more easily. Indirect immunofluorescence assays showed IgG antibodies to M. curtisii at significantly (p less than 0.01) higher titres than to M. mulieris in women with bacterial vaginosis. The titres were higher in patients with bacterial vaginosis than in women without vaginosis and healthy men. No antibodies to Mobiluncus spp. of secretory IgA type were found in vaginal washings. These results indicate that M. curtisii is a more virulent species than M. mulieris, and agree with reports of M. curtisii found in postoperative and extragenital infections.

Adult↗

A 10-year survey of clinically significant blood culture isolates and antibiotic susceptibilities from adult patients with hematological diseases at a major Swedish hospital.

In patients treated with cytotoxic drugs granulocytopenia and septicemia are commonly seen. In this 10-year survey 324 blood culture isolates from 184 patients with hematological diseases and septicemia were studied. The distribution of microbiological diagnoses in patients with hematological diseases as well as acute leukemia 1980-1986 was significantly different (p less than 0.01) from an unselected blood culture material from the same period. The differences are mainly seen between Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and staphylococci. The microbiological spectrum for patients with hematological disease 1987-1989 was also significantly different (p less than 0.05) from the spectrum of the same group of patients 1980-1986 due to higher frequencies of coagulase-negative staphylococci and alpha-streptococci and lower frequency of E. coli in the latter period. 40% of the isolates were gram-positive cocci during the first period and increased to 50% during the second period. The susceptibility testing indicates that trimethoprim/sulfonamide is not as good a choice as ciprofloxacin or norfloxacin for oral antibiotic prophylaxis. For intravenous therapy imipenem/cilastatin or the combinations of an aminoglycoside/piperacillin or aminoglycoside/third generation cephalosporin have advantages over aminoglycoside/trimethoprim/sulfa in combination. However, addition of isoxazolylpenicillin or vancomycin now seems necessary to cover the increasing part of gram-positive bacteria causing septicemia in patients with hematological disease.

4-Quinolones↗

Survey of blood culture isolates in an area of Sweden from 1980 to 1986.

To demonstrate the local epidemiological situation with respect to septicemia in an area of Sweden, a survey was made of all blood cultures performed in the county of Orebro (270,000 inhabitants) from 1980 to 1986. From these blood cultures 4,057 organisms presumed clinically significant were isolated which gives an annual incidence of 215 isolates per 100,000 inhabitants. The two most frequently isolated species were Escherichia coli (24.6%) and Staphylococcus aureus (16.9%). Only minor annual variations in the frequency of different species was observed. An increasing tendency in the isolation rate of Pseudomonas aeruginosa and enterococci since 1980 was noted. Comparison of the findings of the present study with those of other studies demonstrated differences between geographical areas and time-periods. Repeated monitoring of the local spectrum of organisms isolated from blood cultures and, if necessary, adjustment of the routine antibiotic regimen is thus recommended.

Enterobacteriaceae Infections↗

A comparison between Bactec aerobic resin and hypertonic blood culture media.

The presence of antimicrobial agents in patients' blood is thought to represent an important source of false-negative blood cultures. This has led to the incorporation of agents with inhibitory effects on antimicrobial drugs into culture medium. In the present study, Bactec aerobic resin-containing blood culture medium was compared with Bactec hypertonic blood culture medium. 504 patients receiving cytostatic and/or antibiotic treatment were studied. Sensitivity calculations on detection of bacteremia in these patients gave 0.91 for the resin medium and 0.79 for the hypertonic blood culture system and showed a significant difference (p = 0.016). In addition, the resin-containing system more rapidly detected positive cultures than the hypertonic system.

Bacteria↗

A reference procedure to study chemiluminescence induced in polymorphonuclear leukocytes by Neisseria meningitidis.

Luminol-enhanced chemiluminescence (CL) was used to study the ability of various strains of Neisseria meningitidis (MC) to induce oxidative metabolism of polymorphonuclear leukocytes (PMNL); an indirect measure of phagocytic activity. To circumvent variations related to different PMNL donors, a MC serogroup X strain was used as a control for indexing the CL responses induced by other MC strains. This procedure, with pooled serum from healthy blood donors to standardize opsonising conditions, gave reproducible and comparable results, irrespective of PMNL donors. Under these conditions, there was a highly significant difference between pathogenic and non-pathogenic MC strains as regards their ability to induce CL responses (p less than 0.001). The results indicated that the differences were due partly to opsonizing antibodies, partly to other differences related to pathogenicity of tested MC strains. These differences in leukocyte/MC interaction were also confirmed by phagocytic-killing experiments. The index procedure of CL measurements may be a suitable method to study the appearance of natural immunity to MC disease, as well as the pathogenicity of particular MC strains.

Antibodies, Bacterial↗

Antibiotic therapy in pneumonia: a comparative study of parenteral and oral administration of penicillin.

An open, randomized study of treatment of radiologically verified community-acquired pneumonia is described. 33 patients were treated with phenoxymethylpenicillin orally in an average dose of 2 g every 8 h, and 36 patients were treated intravenously with benzylpenicillin 3 g every 8 h. When temperature was normalized the antibiotic dose was reduced in both groups to oral phenoxymethylpenicillin in an average dose of 1 g every 8 h. 24 and 26 patients in respective groups completed 10 days of therapy. No statistically significant differences between the two groups were found when compared for duration of fever, hospital stay, CRP, ESR, leukocyte counts and X-ray normalization. In spite of the low number of patients included in this study it gives a clear indication that treatment of pneumonia with penicillin by the oral route results in the same outcome as parenteral treatment when patients suffering from vomiting, diarrhoea and severe illness with respiratory distress are excluded. In addition, oral treatment is cheaper than parenteral and more simple to manage.

Administration, Oral↗

Water-melon as a vehicle of transmission of shigellosis.

An epidemic of Shigella sonnei infection is described in which the only common source of infection was the ingestion of water-melon. Bacteriological studies demonstrated that S. sonnei bacteria injected into water-melons could multiply to infective doses. Therefore water-melons should not be excluded as a possible source of S. sonnei infection.

Adult↗

Diagnosis of pneumococcal pneumonia by detection of antigen in saliva.

A sandwich enzyme-linked immunosorbent assay was used for the detection of pneumococcal C polysaccharide in saliva samples from patients with radiologically verified pneumonia. In 16 of 29 patients (55%) with pneumococcal pneumonia, as verified by conventional culture methods, the antigen was present in saliva specimens. The test was negative in 35 of 36 patients (97%) with non-pneumococcal pneumonia and in all saliva samples from a control group, consisting of 25 patients with no signs of respiratory disease. It is concluded that the detection of pneumococcal C polysaccharide in saliva offers a valuable complement to conventional diagnostic methods for pneumococcal pneumonia.

Antigens, Bacterial↗

Randomized comparison of aztreonam and cefuroxime in gram-negative upper urinary tract infections.

In order to evaluate the efficacy and safety of aztreonam in hospitalized patients with upper urinary tract infections (UTI), a comparative clinical study with cefuroxime was performed. 62/60% (aztreonam/cefuroxime) of the patients had a complicating factor, mostly obstructive uropathy. I.v. bolus injections were used at a dose of 1 g aztreonam or 1.5 g cefuroxime t.i.d., for a mean of 8.2 days (range: five to 14 days) except in patients with bacteraemia, who received a mean of 10.3 days (range: seven to 13 days) of therapy. 89% of the patients treated with aztreonam and 87% of those who received cefuroxime showed clinical cure and the bacteriological cure rate at one week post-therapy was 70% and 73% in the respective groups. The relapse/reinfection rate was high with both drugs; bacteriological cure at one month post-therapy was only 43% after aztreonam and 40% after cefuroxime. This suggests that these infections may need longer treatment times. Superinfections, mostly asymptomatic urinary colonization, occurred in 7% and 3%, respectively, and adverse reactions in 23% and 12%, respectively, of the patients treated with aztreonam or cefuroxime, the majority being mild and reversible and only 3% and 3%, respectively, requiring discontinuation of the therapy. The t 1/2 for aztreonam following a 1 g i.v. bolus was 2.0 h in six patients with creatinine clearance above 80 ml/min and 3.0 h in seven patients with creatinine clearance between 35-75 ml/min.

Adolescent↗