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Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y., Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews., Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently., Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

We report two cases of Streptococcus pneumoniae-associated hemolytic uremic syndrome (SP-HUS) caused by serotype 3. One case occurred in an unvaccinated boy and 1 in a girl vaccinated with the 13-valent pneumococcal conjugate vaccine. SP-HUS must be considered in children, and conjugate vaccines may be less effective against serotype 3 than other serotypes.

Invasive pneumococcal infections in 777 adults caused by 'invasive' (1, 7; n=187), 'paediatric' (6, 9, 14, 19, 23; n=304) and other (n=286) serogroups were compared. Infections caused by 'invasive' strains caused pneumonia more often than other serogroups and were more often isolated from younger patients without concomitant conditions and had lower case-fatality rate than 'paediatric' and other strains. The 2 latter groups differed little from each other. Infections caused by strains in the 7-valent pneumococcal conjugate vaccine differed little from infections caused by non-vaccine types indicating that widespread use of this vaccine will not markedly change the clinical characteristics of invasive pneumococcal infections in adults.

The antibiotic susceptibility of 297 invasive isolates of group B streptococci (GBS) to a panel of 12 antibiotics was analysed using the E-test. The isolates (from 123 neonates and 174 adults) were collected from south-west Sweden during the 2 periods 1988-1997 and 1998-2001. The breakpoints of the Clinical and Laboratory Standards Institute were used. All isolates were sensitive to cefotaxime, meropenem, linezolid, vancomycin, moxifloxacin and quinupristin-dalfopristin. Two strains displayed a slightly decreased susceptibility to penicillin G (MIC 0.25 microg/ml) also when tested by the broth dilution method. Two per cent were resistant to erythromycin and 1% to clindamycin. Strains with intermediate sensitivity to erythromycin and clindamycin increased over the 2 study periods. 68% were resistant to doxycycline, and the resistance rate for doxycycline increased over the 2 study periods. No strain was resistant to trimethoprim-sulfamethoxazole. Serotype V dominated among strains with intermediate susceptibility to erythromycin and clindamycin. There were no other relationships between serotypes and decreased sensitivity to any agent. There were no significant differences in susceptibility to any agent tested between strains isolated from neonates and adults. In conclusion, penicillins remain the drug of choice in the region but with the increasing rates of intermediate susceptibility to both erythromycin and clindamycin, antibiotic sensitivity analysis should be performed on the GBS isolates from penicillin-allergic patients.

Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC >0.06 to < or = 1.0 mg/l), but none were R (MIC >1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non-susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7-valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden.

Pneumococci isolated from blood and cerebrospinal fluid from 1998 to 2001 in 2 counties in south-west Sweden were serotyped with the capsular reaction test. Of the 836 strains, 353 (42%), 598 (72%) and 789 (94%) belonged to serotypes included in the 7- and 11-valent pneumococcal conjugate vaccines and in the 23-valent polysaccharide vaccine, respectively. The most common serotype was type 1 (119 isolates) followed in descending frequency by serotypes 7F, 9V, 14, 4 and 12F (90-49 isolates per serotype). The coverage rates of the 7- and 11-valent conjugate vaccines among 58 strains isolated from children and adolescents 0-19 y of age were 46% and 93%, respectively. A comparison of clinical characteristics of infections caused by different serotypes showed that types 1 and 7F were less commonly associated with severe underlying diseases, that patients infected with these serotypes were younger than the average and, thus, had a lower case-fatality rate.

In a retrospective study, the incidence, clinical manifestations, concomitant conditions and case fatality rate were studied in patients with invasive pneumococcal infections in the Göteborg area of Sweden during 1981-95, when the pneumococcal polysaccharide vaccine was available but little used. Patients were identified from the records of the Departments of Clinical Bacteriology and from the computer-based hospital discharge registers of the relevant departments. Individual case records were found for 876 patients with invasive pneumococcal infections verified by cultures from blood, cerebrospinal fluid or other sterile body fluids. A study from the same area with the same design covering the years 1964-80 has previously been published. There was an increase in total incidence from 5.3 to 10.3 cases/100,000/y from the previous to the present study. This increase was due to an increase in patients with non-meningitic infections aged > or = 60 y. The incidence of meningitis was virtually unchanged (1.4/100,000/y), as was the incidence of non-meningitic infections in individuals < 60 y. There were no other important changes between the 2 studies, which confirm that invasive pneumococcal infections have the highest incidence rates in children < 2 y and in the elderly, that a wide variety of underlying conditions are seen in the patients and that the case fatality rate, 15% in the present study, is still high.

In order to determine the aetiology of acute epiglottitis in adults, blood cultures, paired sera and a urine sample were obtained from 54 patients with fever and epiglottitis visualized by indirect laryngoscopy or by direct fibreoptic nasolaryngoscopy. Antibodies were determined against the capsular polysaccharide of Haemophilus influenzae type b (Hib), 3 pneumococcal antigens (a mixture of 23 capsular polysaccharides, C-polysaccharide and pneumolysin) and antistreptolysin O. Acute sera were examined by the polymerase chain reaction (PCR) for DNA of Hib and pneumococci. The urine samples were examined for Hib capsular antigen. Blood cultures were positive in 15 patients. In another 16, serology and/or PCR verified the aetiology. Hib was the cause in 14, pneumococci in 12 and group A streptococci in 5 patients. The aetiology remained unknown in 23/54 patients (43%). In conclusion, the addition of serology and PCR to blood cultures doubled the possibilities of verifying the aetiology of acute epiglottitis in adults.

The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

The serum IgG antibody response and decrease to 3 Bordetella pertussis antigens was compared in children with pertussis. Sera were obtained at the first clinical visit and 1, 3 and 12 months later from 89 children with > or = 3 weeks of paroxysmal cough. IgG antibodies to pertussis toxin (PT), to filamentous hemagglutinin (FHA) and to pertactin were determined with ELISA. Of 54 children with culture-confirmed pertussis or culture-confirmed familial exposure, 45 (83%) had a significant (> or = 3 fold) increase in PT IgG and 40 (74%) in FHA IgG antibodies, while only 29 (54%) had a significant increase in pertactin IgG antibodies. Significant decreases in PT, FHA and pertactin IgG antibodies were found in 34 (63%), 9 (17%) and 28 (52%) children, respectively. In the remaining 35 who did not have culture-confirmed disease, significant PT and/or FHA IgG antibody increases (criteria for pertussis according to the WHO definition) were found in 17 (49%). Only 6 of these 17 children had a significant pertactin IgG antibody increase. Of the remaining 18 children (who did not fulfil WHO criteria for pertussis), significant decreases in PT and/or FHA IgG antibodies were found in 13. We conclude that a serum IgG reaction to PT and FHA occurs in almost all children with pertussis. An increase in pertactin IgG antibodies occurs less frequently than against PT and FHA. Significant decreases in PT or FHA IgG antibodies in children with clinical pertussis might be of use as a diagnostic criterion in children brought late for examination.

A cost-benefit analysis of general vaccination of infants with a conjugated Haemophilus influenzae type b (HIB) vaccine was performed. Information on incidence and prognosis of HIB meningitis and acute epiglottitis in children was obtained from nation-wide retrospective studies covering the years 1981-83, when the birth rate was approximately 93,000 per year. The annual cost for hospitalization, neurologic and auditory sequelae and parents' absence from work amounted to 54 million Swedish crowns (SEK). A mean of 6 children died every year. Inclusion of value of lives lost added SEK 72 million to the cost of disease. With vaccine prices (approximately SEK 125/dose) and birth rate (approximately 120,000 per year) prevailing in 1993, vaccine costs would be SEK 45 million, provided that 3 doses are sufficient to offer protection close to 100%. Other costs for vaccination, e.g. physicians' and nurses' time, needles and syringes, are negligible, since the vaccine can be given at the same time as other infant vaccinations at already existing Child Health Centres. In conclusion, general vaccination of infants against HIB is cost-effective, saves lives and reduces human suffering.

In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly.

The glomerular filtration rate (GFR) was estimated from serum creatinine concentration in patients in whom the individual relation between GFR and serum creatinine had been previously determined. 51Cr-EDTA plasma clearance was used as reference method for GFR. The relation between 51Cr-EDTA clearance and estimated GFR was determined from 340 investigations in 197 adult patients with a variety of infectious and internal diseases. The imprecision of estimated GFR was 46% (1 CV) at 20 ml/min, 23% at 45 ml/min, 20% at 75 ml/min and 18% at 110 ml/min. This poor precision was probably due to the fact that many patients with acute infectious diseases, congestive heart failure, diabetes mellitus, etc., have an unstable renal function and therefore their creatinine distribution is not under steady state. This must always be considered when serum creatinine is used to estimate GFR.

The liver function was studied in 15 patients before and during treatment with cefuroxime. Four elderly patients had a prolonged half-life of galactose at admission but they all showed declining values during the cefuroxime treatment. Only in one patient did the galactose half-life increase during treatment (from 14 to 25 min.). This patient was an old diabetic who also had prostatic cancer. Cefuroxime treatment seems to be well tolerated also in patients with signs of impaired metabolic liver function at start of treatment.

In 107 patients with lower respiratory tract infections, counterimmunoelectrophoresis (CIE) of blood and sputum, bacterial cultures of blood, sputum and nasopharyngeal secretion, and enzyme-linked immunosorbent assay (ELISA) for antibody determination were performed, with special reference to pneumococci and Haemophilus influenzae. For pneumococci CIE of sputum was superior to culture especially in antibiotic-treated patients. The clinical significance of a positive CIE of sputum was supported by close correlation to significant antibody increase. The usefulness of CIE regarding H. influenzae was more difficult to evaluate.

The glomerular filtration rate measured by 51Chrome-EDTA and serum half life of cefoxitin were followed in patients with preexisting moderate renal impairment. The patients were treated with cefoxitin for two to three weeks because of chronic serious infections. The dose used in patients with an initial clearance of more than 40 mg/ml was 1 g three times daily giving a mean peak concentration of 100 microgram/ml. Seven patients were treated with cefoxitin alone and twelve with cefoxitin and furosemide (80 mg daily orally). The glomerular filtration rate did not change significantly during treatment time. There were no signs of accumulation of cefoxitin as serum half life of the drug remained unchanged both in patients treated with and without furosemide concurrently.

In order to determine whether healthy adults can be of importance for the spread of pertussis the nasopharyngeal flora of 391 healthy individuals working in close contact with children was investigated during the height of a pertussis epidemic. Only 1 carrier of Bordetella pertussis was found, even though all individuals were exposed to the organism during the study period through their work.

In a prospective, randomized, comparative study, the renal, hepatic and gastrointestinal toxicity and effects on the vitamin K dependent coagulation factors of gentamicin and cefotetan were compared. Gentamicin, which in all but one patient was combined with a penicillin, was found to cause a significant decrease of glomerular filtration rate (GFR) after 1 week of treatment. In 6/14 patients a further decrease of GFR was found during the week following the last treatment day. The renal proximal tubular cells were affected by gentamicin, as evident from significant increases in urinary activity of 2 tubular enzymes, alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as rises of urinary beta 2-microglobulin. Changes in GFR and tubular function were reversible. No statistically significant changes of these variables were seen with cefotetan. One cefotetan treated patient developed diarrhoea of moderate severity and 2 patients in the same group developed minor increases of liver transaminases. A small but statistically significant decrease of the activity of the vitamin K dependent coagulation factors occurred during cefotetan treatment. No gastrointestinal or hepatic adverse reactions were observed in the gentamicin treated patients.

Side effects of cefoxitin and cefuroxime were noted in 2 different studies during intravenous treatment for at least 14 days. In the cefoxitin group of 33 patients thrombophlebitis was observed in 3 cases and diarrhoea in 4 cases. In the cefuroxime group of 31 patients 1 case of thrombophlebitis was noted and 5 cases of diarrhoea occurred. Most patients with diarrhoea had decreased renal function or received higher dosage of the antibodies than the other patients.

215 strains of Streptococcus pneumoniae isolated from blood or cerebrospinal fluid at 3 different laboratories in Sweden were serotyped by coagglutination and subtyped by the capsular reaction test. 78% of the strains belonged to serotypes which are included in or completely cross-immunogenic with serotypes included in the 14-valent vaccine while serotypes included in the 23-valent vaccine covered 89% of the isolates. Types 7F, 14 and 33F, which cannot be detected by counterimmunoelectrophoresis constituted 19% of all strains.