[Decreasing vaccination rate--increasing risk of epidemics].
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Biomedical subjects
Publications and source records attributed to N Høiby.
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We report survival data for Danish center-treated cystic fibrosis (CF) patients, covering the period 1974-1993 and using cross-sectional cumulative survival probability based on annual age-specific mortality rates. Analyses by age and by years after diagnosis were made. No significant differences were noted in the survival probability when patients were grouped according to sex or absence/presence of meconium ileus. The annual mortality rate for 1989-1993 was 0-1.2%. Using the age-specific mortality rate for 1989-1993, we were unable to calculate the median survival probability because the curve did not fall below 50% (age up to 45 years); however, it was possible to show that the survival probability for a newborn CF child to reach his 45th birthday was 80.4%(confidence interval 76.5-84.6%). The median age at diagnosis was 0.63 years with no sex difference. The probability of surviving 40 years after the diagnosis of CF was made was 83.3% (confidence interval 80.1-86.6%). This is considerably higher than any other published survival probability. An early anti-Pseudomonas aeruginosa treatment regimen seemed important in achieving the observed improved survival.
Burkholderia cepacia isolates from nine of the ten Danish cystic fibrosis (CF) patients known between 1975 and the present day to carry this organism were investigated. Eight distinct genotypes were found with polymerase chain reaction ribotyping and pulsed-field gel electrophoresis. The results indicate that there is little patient-to-patient cross-infection with Burkholderia cepacia within the Danish CF population, even though the majority of patients attend the same CF clinic on a regular basis.
A three-month prospective surveillance study was undertaken in four dialysis centres to establish the prevalence of Staphylococcus aureus carriage in a Danish population of patients on haemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of months in dialysis, hospital and ward were registered on a precoded form. Standardized nose and four skin swabs (axillae, groins, perineum) were performed on the first day of the survey. After one and two months, nose swabs were collected. Infections were registered and cultures were sent for phage-typing together with the S. aureus strains isolated from the swabs; 59.5% of HD patients and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD, peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by S. aureus (34.8%). More than two thirds of the infections in HD patients were related to intravascular catheterization. The most serious infection was septicaemia, in all cases due to S. aureus. S aureus infections occurred significantly more frequently among carriers (P = 0.005), and more than half the patients were infected by the same or possibly the same strain as they carried in the nose or on skin. Different regimens for the elimination of S. aureus carriage in dialysis patients are discussed. A policy for risk assessment of patients should be developed, and the elimination of S. aureus carriage before dialysis should be encouraged. Controlled trials comparing the cost-effectiveness of recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose swabs are reliable indicators of carriage in dialysis patients.
In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P = 0.004) and controls (P = 0.003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) (> or = 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes (> or = 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN-gamma-treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.
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Forty Pseudomonas aeruginosa strains, previously characterized by pulsed-field gel electrophoresis, were ribotyped with EcoRI, BamHI, ClaI, and PvuII. Ribotyping with PvuII proved to be as discriminatory as pulsed-field gel electrophoresis with XbaI or DraI while EcoRI and BamHI were not. ClaI contributed further ribotypes, some of which might be due to a transposable element.
BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry. A longitudinal study on 43 consecutive patients with cystic fibrosis who developed chronic lung infection with P aeruginosa was performed. RESULTS: IgG subclass a beta ab appeared in all patients with chronic infection with P aeruginosa. Eleven years after the onset of infection all the patients had IgG1, 79% had IgG4, 56% IgG2, and only 16% of the patients had IgG3 a beta ab. The IgG1 and IgG4 a beta ab appeared first, and more than 50% of the patients were IgG1 and IgG4 a beta ab positive within 2-3 years of the onset of infection, but IgG2 positivity only appeared after seven years and IgG3 remained absent from most of the patients. The median a beta ab levels increased during chronic infection: 100-fold for IgG1, 22-fold for IgG2, and 45-fold for IgG4. A 16-fold increase in the IgG3 a beta ab levels was detected in the six patients who developed IgG3 a beta ab. In the first four years of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor.
The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable.
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A case of cholera imported to Denmark from the Pacific is presented. The patient was successfully treated with rehydration and antibiotics. A survey of the ongoing seventh pandemic of cholera is given and the possible emergence of a new eighth pandemic is discussed. Guidelines for prophylactic and therapeutic measures are discussed. Although V. cholerae colonies can be recognized on routine cultivation media, low numbers require selective media, and this is not included in routine investigations of stools for pathogens.
Heat-stable opsonins from sera of cystic fibrosis (CF) patients were investigated for their ability to activate complement. Complement activation by Pseudomonas aeruginosa after opsonization with patient serum was examined in a complement-consumption assay. Absorption of patients' sera with formalin-treated and boiled bacteria removed specific antibodies and the complement activation decreased. We found a positive correlation between serum complement-activation ability and IgG3 antibody levels to lipopolysaccharide (LPS), alginate, and a crude mixture of P. aeruginosa antigens (sonicate) in a group of patients with high levels of anti-Pseudomonas precipitins. In the same group of patients a significant negative correlation was found between complement activation and lung function. Eighteen patients have been followed longitudinally with serum samples covering the pre-infection, the early, and the late stages of chronic infection. Patients with poor lung function showed significantly higher levels of complement-activation capacity. We conclude that patients with high levels of specific IgG3 antibodies are able to induce a high level of complement activation and then develop more aggressive pulmonary tissue damage, probably secondary to local immune complex formation.
The prevalence and antibiotic sensitivity patterns of bacteria collected consecutively from medical and surgical intensive care units (ICUs) and from hematology/oncology units in nine hospitals in Denmark were determined and compared to data collected simultaneously in 12 other European countries. Bacterial isolates from 794 Danish patients were tested and compared to 8,625 isolates from European patients. The minimal inhibitory concentrations of eight different antibiotics were determined using a microdilution plate. Similar to findings in European countries, the most common source of bacterial isolates in Danish units was the respiratory tract (49%), followed by blood (18%), urinary tract (14%) and surgical wounds (10%). Staphylococcus aureus was the most prevalent respiratory organism in Danish units, whereas Enterobacteriaceae and Pseudomonas aeruginosa dominated in other countries. In blood, Escherichia coli was most prevalent in Denmark while coagulase-negative staphylococci were predominant in other countries. Urinary tract isolates were dominated by Escherichia coli in both Denmark and the other countries, but Enterococcus faecalis and Pseudomonas aeruginosa were more frequently isolated in the other countries. Staphylococcus aureus was the most frequent wound isolate in Denmark, while Enterobacteriaceae other than Escherichia coli dominated in other European countries. Thus, in Denmark Escherichia coli and Staphylococcus aureus, followed by Pseudomonas aeruginosa and Klebsiella spp. (from ICUs) or Enterococcus spp. and Klebsiella spp. (from hematology/oncology units), are the most prominent pathogens in these units today. Indicator organisms of antibiotic consumption (Pseudomonas aeruginosa and methicillin-resistant coagulase-negative staphylococci and Staphylococcus aureus) were more frequent in other European countries than Denmark. In general the Danish isolates were more sensitive to antibiotics than the European isolates.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to identify the possible reservoirs and routes of cross-infection with Pseudomonas aeruginosa, samples were collected during a six-week period in autumn 1992 from patients, their visiting parents, staff and the inanimate environment of the Danish Cystic Fibrosis (CF) Centre and from a control ward with common paediatric diseases. All the P. aeruginosa strains were phage typed and serotyped. From 240 CF patients, 310 strains of P. aeruginosa were isolated, and of these 283 (91.3%) belonged to the polyagglutinable phenotype, most often with a short phage type (31/188 or 109). P. aeruginosa was isolated from only six (0.6%) of 1000 swabs taken from the environment. These six environmental strains and 20 P. aeruginosa strains from CF patients with identical serotype and phage type were examined with pulsed field gel electrophoresis. None of the patients harboured strains similar to the environmental strains, indicating the present isolation procedure and hygienic precautions were effective in our CF centre, and prevented contamination of the environment with P. aeruginosa.
Cross-infection with Pseudomonas aeruginosa and Pseudomonas cepacia has been shown sometimes to occur between cystic fibrosis (CF) patients in some CF centres, in some summer camps and during some social contacts between CF patients. Cohort isolation and improved hygienic precautions, however, have successfully been employed in some CF centres resulting in a decrease or elimination of cross-infection. Chronic P. aeruginosa infection is in most CF patients preceded by a period of intermittent colonization. Early aggressive chemotherapy (oral ciprofloxacin and nebulized colistin for 3 weeks) every time P. aeruginosa is detected in sputum has significantly decreased the incidence of new chronic infection in CF patients. Chronic P. aeruginosa infection can be treated by "maintenance chemotherapy" (= chronic suppressive chemotherapy). The principle is to restore lung function repeatedly by regular 2-week courses of intensive intravenous treatment every 3 months in the CF centre and adding daily inhalations of colistin between the courses, and sometimes also by giving oral ciprofloxacin during these intervals to unstable patients. Eradication of P. cepacia infection is virtually never obtained by antibiotic treatment with, e.g., ceftazidime and tobramycin or co-trimoxazole. Chronic suppression with doxycyclin or co-trimoxazole may give rise to some improvement in the clinical symptoms.
Chromosomal beta-lactamase production is considered to be the most important resistance mechanism of Pseudomonas aeruginosa against beta-lactams. Recently we have detected serum and sputum antibodies against P. aeruginosa chromosomal beta-lactamase (a beta ab), using immunoblotting techniques. In this study we have developed an enzyme-linked-immunosorbent assay to measure serum a beta ab response in 124 cystic fibrosis patients in a cross-sectional study and in 54 cystic fibrosis patients in a longitudinal study. The a beta ab response occurred after a median of 3 years following onset of chronic infection and was significantly higher (P < 0.0002) in patients chronically infected with resistant strains than in those from whom resistant strains were occasionally isolated. The a beta ab levels correlated (r = 0.51, P = 0.0001) with the number of beta-lactam courses. A 14 fold increase in a beta ab levels occurred during the 14 year period covered by the longitudinal study. The results of this study show that a beta ab to P. aeruginosa is a specific marker for resistance development of P. aeruginosa to beta-lactams.