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Objectives: To study effects of the introduction of pneumococcal conjugate vaccines (PCV) on the interspecies dynamics of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in preschool children with respiratory tract infection., Methods: Nasopharyngeal samples from children aged ≤6 years with upper respiratory tract infection (n = 14 473) in South Sweden were analysed during 14 consecutive years, 5 years before and 9 years after PCV introduction. The yearly prevalence was calculated, and multivariate count regressions between prevalence and estimated yearly proportions of vaccinated children were performed. Associations between pneumococcal serotypes and the other pathogens were assessed., Results: When comparing the prevaccine period with the years after introduction, the prevalence of S. pneumoniae decreased by 65.2% (16.4 to 5.7 per 1000 individuals; p < 0.001), whereas M. catarrhalis and H. influenzae decreased by 52.1% (21.5 to 10.3 per 1000 individuals; p < 0.001) and 46.6% (13.6 to 7.3 per 1000 individuals; p < 0.001), respectively. In multivariate negative binomial regressions adjusted for yearly numbers of samples taken, S. pneumoniae and M. catarrhalis were significantly negatively associated with increasing vaccine coverage proportions (adjusted prevalence ratio (aPR) = 0.17; p < 0.001 and aPR = 0.48; p < 0.001, respectively), whereas H. influenzae (aPR = 0.75; p = 0.17) was not. In addition, the proportion of cultures positive for S. pneumoniae as well as M. catarrhalis was significantly lower in the postvaccine period compared to the prevaccine period, while this was not the case for H. influenzae. A significant positive association between certain PCV serotypes and simultaneous growth with M. catarrhalis was observed., Conclusions: After introduction of PCV, the prevalence of M. catarrhalis in addition to S. pneumoniae in children with respiratory tract infection decreased; this was also the case after adjusting for reduced numbers of samples taken. This may partly be attributed to a positive association between PCV serotypes and M. catarrhalis., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Several different IgA-proteases exist in Haemophilus influenzae. The variants have been suggested to play differential roles in pathogenesis, but there is limited information on their distribution in clinical isolates. The objective of this study was to investigate the distribution of IgA-protease genotypes in H. influenzae and assess the association between IgA-protease genotype and type of clinical infection., Methods: We performed PCR-screening of the IgA-protease gene variants in two cohorts of clinical H. influenzae. The first cohort consisted of 177 isolates from individuals with respiratory tract infection in January 2010, 2011 and 2012. Information on age, gender and clinical infection was available in this cohort. The second cohort comprised 53 isolates, including NTHi from bloodstream, cerebrospinal fluid (CSF) and urogenital origin as well as encapsulated isolates respresenting all capsule types. We assessed associations between IgA protease genotype and clinical predictors using basic statistical tests of association as well as regression analysis., Results: The igaB gene was found in 46% of isolates in the respiratory tract cohort, and no evident trend could be seen during the study years. However, the igaB gene was significantly less common among invasive isolates (19%), p = 0.003 (Fischer's exact test), even when encapsulated isolates were excluded (21%), p = 0.012. A significantly negative association between bacteraemia and igaB genotype remained after adjusting for covariates. We did not identify a significant association between IgA-protease gene variants and type of respiratory tract infection, but isolates with an igaA2 genotype were overrepresented in pre-school children., Conclusions: The distribution of IgA-protease gene variants in Swedish H. influenzae highlighted the widespread abundance of the igaB in isolates from cases of respiratory tract infection, but the igaB gene variant was significantly less common in invasive (bloodstream and CSF) isolates of H. influenzae compared with respiratory tract isolates.

Objectives: Increasing incidences of non-typeable Haemophilus influenzae (NTHi) with β-lactam resistance mediated through mutations in penicillin-binding protein 3 (BLNAR or rPBP3) have been observed in the past decades. Recently, an rPBP3 NTHi sequence type (ST) 14 with PBP3 type IIb/A caused a disease outbreak in a nursing home in Sweden with severe outcomes, indicating increased bacterial virulence. In this prospective observational study, the epidemiology and clinical significance of the corresponding clonal group (ST14CC-PBP3IIb/A) in Skåne, Sweden was investigated., Methods: ST14CC-PBP3IIb/A isolates were identified through partial multilocus sequence typing and ftsI(PBP3 gene)-sequencing of prospectively collected H. influenzae from patients with respiratory tract or invasive infections (n=3262) in 2010-2012. Data on type of infection, hospitalization and outcomes were analysed, and the geographical distribution of isolates from different groups was investigated., Results: Isolates belonging to ST14CC-PBP3IIb/A constituted 26% (n=94/360) of respiratory tract rPBP3 NTHi. From mapping of patient addresses, a dynamic geographical spread was apparent during the study period. Furthermore, patients with infections by ST14CC-PBP3IIb/A isolates had higher hospitalization rates compared with patients infected with other rPBP3 NTHi (14/83 versus 21/255, p 0.025) and to a group of patients infected with susceptible NTHi (14/83 versus 13/191, p 0.010). ST14CC-PBP3IIb/A isolates constituted 25% (n=2/8) of invasive rPBP3 NTHi during the study period., Conclusions: Our investigation suggests that the ST14CC-PBP3IIb/A clonal group is associated with increased clinical virulence, resistance to several antimicrobial agents, and is persistent over time. We conclude that virulence varies between different NTHi, and that NTHi disease may be more dependent on bacterial factors than previously recognized., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: During October 2011 several residents and staff members at a long-term care facility (LTCF) for elderly fell ill with respiratory symptoms. Several of the residents required hospitalization and one died. Non-typeable Haemophilus influenzae (NTHi) was identified as the causative pathogen., Methods: A descriptive analysis of the outbreak and countermeasures was performed. For each identified bacterial isolate implied in the outbreak, standard laboratory resistance testing was performed, as well as molecular typing and phylogenetic analysis., Results: The identified H. influenzae was beta-lactamase negative but had strikingly high MIC-values of ampicillin, cefuroxime and cefotaxime. All isolates displayed the same mutation in the ftsI gene encoding penicillin-binding protein (PBP) 3, and all but one were identified as sequence type 14 by Multilocus Sequence Typing (MLST). In total 15 individuals in connection to the LTCF; 8 residents, 6 staff members and one partner to a staff member were colonized with the strain., Conclusion: This report illustrates the existence of non-typeable H. influenzae with high virulence, and furthermore emphasizes the importance of continuous surveillance of possible outbreaks in health care facilities and prompt measures when outbreaks occur.

Conclusion: Although children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV) had fewer episodes of acute otitis media (AOM), this trial was unable to prove a simultaneous decrease in nasopharyngeal carriage., Objective: Carriage rates of AOM pathogens in the nasopharynx are high among children, and colonization is the first step towards infection. The possible impact of PCV on carriage is therefore of interest, particularly in children with recurrent AOM. The aims of this study were to examine the effect of heptavalent PCV on carriage of AOM pathogens in children at high risk of developing recurrent disease, and to monitor carriage of resistant pathogens in vaccinated and unvaccinated children., Methods: A total of 109 children with an onset of AOM before 6 months of age, 89 of whom developed recurrent disease, were enrolled in a trial. Fifty-two children were vaccinated and all were closely monitored for 3 years., Results: There was no difference statistically between vaccinated children and controls concerning the carriage of any of the major AOM pathogens. There was evidence of within-child clustering for S. pneumoniae (p = 0.002) and H. influenzae (p < 0.001), indicating that children continued to carry either species over time. Resistance rates were generally low and comparable with national levels.

Objectives: The β-lactamase genes of Haemophilus influenzae are commonly positioned on large integrative and conjugative elements, but a group of blaTEM-carrying small plasmids (4000-6000 bp) with a common structural backbone have recently been characterized. In this study we investigated the epidemiological significance and potential for transfer of this group of small plasmids., Methods: We developed a two-step PCR assay to screen for and type this group of resistance plasmids in H. influenzae. A large collection of respiratory isolates (n = 2845) from south Sweden, obtained from 2009 to 2011, as well as a collection of invasive Swedish H. influenzae from 1997 to 2010 (n = 310) was screened. The distribution of plasmid types among clinical isolates was investigated using multilocus sequence typing (MLST)., Results: In the collection, 15.8% of β-lactamase-producing isolates and 1.4% of total isolates possessed a small plasmid with the signature structure. The plasmids were genetically conserved and widely spread geographically. MLST revealed that the spread of small plasmids occurred by both clonal expansion and horizontal transfer. In vitro experiments suggested that one plasmid type, pN223, can transfer ampicillin resistance to susceptible Escherichia coli., Conclusions: Small β-lactamase-encoding plasmids constitute a significant mechanism for β-lactam resistance in H. influenzae and can spread through clonal expansion of resistant clones as well as through horizontal plasmid transfer.

Haemophilus influenzae (Hi) causes respiratory tract infections and is also considered to be a commensal, particularly in preschool children. Tonsils from patients (n = 617) undergoing tonsillectomy due to chronic infection or hypertrophy were examined. We found that 51% of tonsils were positive for Hi, and in 95% of cases analyzed in detail (n = 39) Hi resided intracellularly in the core tonsillar tissue. Patients harbored several intracellular unique strains and the majority were nontypeable Hi (NTHi). Interestingly, the isolated NTHi bound soluble immunoglobulin (Ig) D at the constant heavy chain domain 1 as revealed by recombinant IgD/IgG chimeras. NTHi also interacted with B lymphocytes via the IgD B-cell receptor, resulting in internalization of bacteria, T-cell-independent activation via Toll-like receptor 9, and differentiation into non-NTHi-specific IgM-producing cells. Taken together, IgD-binding NTHi leads to an unspecific immune response and may support the bacteria to circumvent the host defense.

The proportions of Haemophilus influenzae resistant to ampicillin and other β-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish H. influenzae isolates with resistance to β-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of H. influenzae isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (n = 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested β-lactam were further analyzed in detail. We identified a significantly increased (P = 0.03) proportion of β-lactam-resistant invasive H. influenzae during the study period, which was mainly attributed to a significant recent increase of β-lactamase-negative β-lactam-resistant isolates (P = 0.04). Furthermore, invasive β-lactamase-negative β-lactam-resistant H. influenzae isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MLST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of β-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a β-lactamase gene with a promoter deletion, bla(TEM-1)-PΔ dominated among the β-lactamase-positive H. influenzae isolates. Our results show that the proportions of β-lactam-resistant invasive H. influenzae have increased in Sweden in the last decade.

Introduction of a conjugated vaccine against encapsulated Haemophilus influenzae type b (Hib) has led to a dramatic reduction of invasive Hib disease. However, an increasing incidence of invasive disease by H. influenzae non-type b has recently been reported. Non-type b strains have been suggested to be opportunists in an invasive context, but information on clinical consequences and related medical conditions is scarce. In this retrospective study, all H. influenzae isolates (n = 410) from blood and cerebrospinal fluid in three metropolitan Swedish regions between 1997 and 2009 from a population of approximately 3 million individuals were identified. All available isolates were serotyped by PCR (n = 250). We observed a statistically significant increase in the incidence of invasive H. influenzae disease, ascribed to non-typeable H. influenzae (NTHi) and encapsulated strains type f (Hif) in mainly individuals >60 years of age. The medical reports from a subset of 136 cases of invasive Haemophilus disease revealed that 48% of invasive NTHi cases and 59% of invasive Hif cases, respectively, met the criteria of severe sepsis or septic shock according to the ACCP/SCCM classification of sepsis grading. One-fifth of invasive NTHi cases and more than one-third of invasive Hif cases were admitted to intensive care units. Only 37% of patients with invasive non-type b disease had evidence of immunocompromise, of which conditions related to impaired humoral immunity was the most common. The clinical burden of invasive non-type b H. influenzae disease, measured as days of hospitalization/100 000 individuals at risk and year, increased significantly throughout the study period., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

According to the recommendations of the Swedish Community-Acquired Pneumonia (CAP) guidelines, the selection of empirical antibiotic therapy should be based on the CRB-65 rule. The guidelines recommend empirical therapy directed predominantly against Streptococcus pneumoniae for patients with low CRB-65 scores and broad-spectrum therapy for patients with high CRB-65 scores. In order to study the utility of the recommendations, we analyzed the data from an aetiological study previously performed on 235 hospitalized adult CAP patients at our medical centre. A definite, probable, or possible bacterial aetiology was noted in 194 cases (83%), including 112 cases (48%) with S. pneumoniae aetiology. The following frequencies of definite-probable aetiologies were noted in the patients with CRB-65 score 0-1 (n=155) and CRB-65 score 2-4 (n=80): S. pneumoniae 30% and 35%, Haemophilus influenzae 6.5% and 14% (p=0.063), Mycoplasma pneumoniae 15% and 5.0% (p=0.019), Chlamydophila species 2.6% and 1.2%, Legionella pneumophila 1.9% and 0%, and Staphylococcus aureus 1.3% and 1.2%, respectively. The high frequency of S. pneumoniae in the study supports the recommendations to predominantly cover this bacterium in the empirical therapy of patients with low CRB-65 scores. In the case of treatment failure in these patients, the study indicates that coverage against M. pneumoniae and H. influenzae should be considered.

Objective: To study the etiology of clinically diagnosed community-acquired pneumonia (CAP) in antibiotically naive patients attending a primary care center and treated at their homes., Methods: A three-year prospective study was carried out, and 177 patients presenting with clinical signs of CAP were included. All patients had chest X-rays after inclusion, and 82 (46%) showed infiltrates. Nasopharyngeal swab culture was performed on all patients, and 51% produced a representative sputum sample. Paired sera were obtained from 176 patients., Results: Among the 82 patients with radiographically proven CAP, Streptococcus pneumoniae was detected in 26 patients (32%), Haemophilus influenzae in 23 (28%), Mycoplasma pneumoniae in 15 (18%), and Chlamydia pneumoniae in four (5%). Serologic evidence of a viral infection was found in 13 patients (16%). Among the 95 patients without infiltrates, S. pneumoniae was found in 21 (22%), H. influenzae in 14 (15%), M. pneumoniae in two (2%), and C. pneumoniae in five (5%). Viral infection was detected in 19 (20%) of these 95 patients., Conclusion: In primary care in Sweden, the initial antibiotic treatment in any patient with pneumonia should be effective against S. pneumonia and H. influenzae. In addition, M. pneumoniae should be targeted during recurrent epidemics. C. pneumoniae, and especially Legionella, seem to be uncommon in primary care.

To investigate the management of patients with community-acquired pneumonia (CAP) treated in hospital in Sweden, a multicentre retrospective cohort study was performed with medical record review of 982 patients (mean age 63 y) at 17 departments of infectious diseases at hospitals in Sweden. Information on antimicrobial therapy, demographic characteristics, comorbid conditions, physical examination findings, and laboratory and microbiological test results were recorded. Outcome measures were in-hospital mortality and length of hospital stay (LOS). Cultures were obtained from blood in 80% and from sputum in 22% of the patients. A microbiological aetiology was determined for 23% of the patients, with Streptococcus pneumoniae as the dominating agent (9%). The initial antibiotic treatment was mostly given intravenously (78%). Penicillin (50%) or a cephalosporin (30%) was the most common choice. Both of these drugs were usually given as a single agent. The overall mortality was 3.5% and the mean LOS was 6.4 d. Thus, the outcome was favourable despite the empirical antibiotic treatment having a narrow spectrum compared with the broader approach recommended in most recent guidelines on the management of CAP. These findings suggest that a majority of patients who are hospitalized with moderately severe pneumonia can be treated initially with penicillin alone.

Sensitivity patterns of Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes were studied prospectively in an outpatient population seeking medical advice for respiratory tract infections (RTI) in the Southern parts of Stockholm. In total, 3,214 nasopharyngeal and 1,907 throat swabs were cultured during January-February 1996. 32% of the patients had received antibiotics during the previous year. Reduced penicillin sensitivity in S. pneumoniae was rare (1.3%) and only seen in patients treated with antibiotics during the previous 4 months. Beta-lactamase production in H. influenzae was found in 13.4% of patients who had been treated with antibiotics during the last 4 months and in 7.9% of the others. No resistance (< 1%) to erythromycin was seen in S. pyogenes. In this population-based surveillance, the levels of resistance in common respiratory tract pathogens were thus low and correlated to previous antibiotic treatment. Strict indications for antibiotic treatment in uncomplicated RTI are advocated to maintain a low resistance rate. Penicillin is still the drug of choice in patients without frequent recurrences of RTI in a setting similar to the one studied.

To determine the prevalence of the asymptomatic carriage of drug-resistant Streptococcus pneumoniae (DRSP) by children attending day-care centres in the Stockholm area, nasopharyngeal swabs were cultured from 1129 children and 308 day-care personnel in 36 day-care centres during a 3-week period, from March to April 1995. Approximately 36% of the children were asymptomatic carriers of S. pneumoniae sensitive to penicillin and other antibiotics. The highest prevalence of nasopharyngeal carriage was found in the 2-year-old group (50%), whereas among the 4-year-old children colonization was observed in 42%, and among the 7-year-old children 21% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. In 2 day-care centres, 4 and 5 children, respectively, were found to have DRSP strains in the nasopharynx. The same serotype of DRSP strain was found among the children attending the same day-care centre. During the same period, none of the staff were found to harbour DRSP in the nasopharynx, but 3% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. The patterns of nasopharyngeal colonization by Haemophilus influenzae, Moraxella catarrhalis and Group A streptococci were also studied in 635 children during the same period. 42% of the nasal cultures yielded Moraxella, 32% H. influenzae and 2% Streptococcus pyogenes.

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.

In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (case/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.

This study analyzed the effect of breast-feeding on the frequency of acute otitis media. The protocol was designed to examine each child at 2, 6 and 10 months of age. At each visit nasopharyngeal cultures were obtained, the feeding pattern was recorded and the acute otitis media (AOM) episodes were documented. The analysis was based on 400 children from whom complete information was obtained. They represented 83% of the newborns in the study areas. By 1 year of age 85 (21%) children had experienced 111 AOM episodes; 63 (16%) had 1 and 22 (6%) had 2 or more episodes. The AOM frequency was significantly lower in the breast-fed than in the non-breast-fed children in each age group (P < 0.05). The first AOM episode occurred significantly earlier in children who were weaned before 6 months of age than in the remaining groups. The frequency of nasopharyngeal cultures positive for Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was significantly higher in children with AOM. At 4 to 7 and 8 to 12 months of age, the AOM frequency was significantly higher in children with day-care contact and siblings (P < 0.05 and < 0.01, respectively). The frequency of upper respiratory tract infections was increased in children with AOM but significantly reduced in the breast-fed group.

The antibiotic susceptibility of consecutive isolates of the upper respiratory tract pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, and Staphylococcus aureus, (100 strains of each species collected each year during March through April 1985, 1988 and 1992) to penicillin V, amoxycillin, cefaclor, cefuroxime, doxycycline, erythromycin, and cotrimoxazole was investigated by MIC determination on PDM and PDM II agar. The MICs of the upper respiratory isolates from 1992 supplemented with 100 isolates each of Escherichia coli, Klebsiella spp., Enterobacter cloacae, Proteus mirabilis and Staphylococcus saprophyticus collected during 1992 were determined against the above antibiotics plus cefadroxil, cefpodoxime, roxithromycin, ciprofloxacin, ofloxacin, and BAY Y 3118. Beta-lactamase production was found in 10% of H. influenzae and 80-90% of S. aureus and B. catarrhalis in 1992. Among H. influenzae isolates, non-beta-lactamase-induced resistance to all beta-lactam antibiotics was first detected in 1988 and amounted to 3% of isolates in 1992. Decreased susceptibility of S. preumoniae to penicillin (> or = 0.12 mg/l), co-trimoxazole > or = 32 mg/l, doxycycline (> or = 2 ml/l) and erythromycin (> or = 1 mg/l) was detected in 11%, 7%, and 8%, respectively, in 1992, which is significantly higher than in previous years at the same laboratory. Decreased susceptibility of S. pyogenes to doxycycline and erythromycin was detected in 11% and 9% in 1992. The two most recently developed antibiotics, cefpodoxime and BAY Y 3118, showed high antibacterial activity. The study emphasizes the need to screen for resistance mechanisms such as beta-lactamase production and lowered penicillin affinity.

The prevalence and microbiology of macrophotographically documented denture stomatitis were studied in denture wearers participating in an interdisciplinary health-monitoring project (Koster Health Project) on the Koster islands, Sweden. Upper dentures were used by 26.6% of the adult population, and 59.2% of the denture wearers had stomatitis. Denture stomatitis type I was identified as sialadenitis. The more severe forms of denture stomatitis (types II and III) demonstrated increased recovery of microorganisms in the palatal mucosa in addition to sialadenitis. Only one proband showed increased growth of fungi. Hemophilus spp. and Bacteroides spp. were the predominating microorganisms in stomatitis types II and III. Shifts in the normal oral flora are suggested to be an important factor for the development of denture stomatitis. It is concluded that bacterial colonization on the palatal mucosa may play an important role in denture stomatitis in this relatively healthy population.

Sales of antibiotics have increased in Sweden during the past decade. This has been paralleled by an increase in the frequency of beta-lactamase-producing respiratory tract bacteria. To investigate the effects of regional differences in use of antibiotics on beta-lactamase production in respiratory tract bacteria, we collected nasopharyngeal specimens and information about antibiotic use from 1133 children attending day-care centres in four rural municipalities with low use, and one urban municipality with high use of antibiotics, use being assessed from pharmacy sales. The frequency of beta-lactamase production among isolates of Branhamella catarrhalis and Moraxella nonliquefaciens was significantly higher in the urban municipality. This appeared to be a long-term ecological effect of differences in the level of use of antibiotics between the urban and rural populations, rather than an effect of recent antibiotic treatment of individual patients.

The role of Haemophilus influenzae in acute purulent conjunctivitis was studied during an outbreak among children in day care. Five day-care centers contributed 20 cases and 35 controls. All the children were subjected to culture of the nasopharynx and the eyes. H. influenzae was carried in the nasopharynx of 53% of the children (range between day care centers, 20 to 91%). Of the 20 children with acute conjunctivitis 8 had eye cultures positive for H. influenzae, 2 had Moraxella and the remaining were culture-negative. Ten colonies of H. influenzae were isolated from each positive culture and identified by capsular type, biotype and multi-locus enzyme electrophoresis. All but one of the isolates were nonencapsulated. They belonged to 4 biotypes and 8 electrophoretic types. The same strain was recovered from the eyes and nasopharynx of the symptomatic children, suggesting that the H. influenzae in the eyes originated from the nasopharynx. There was no evidence for spread of the same H. influenzae strains between day-care centers. Even within each center the Haemophilus strains recovered from the eyes varied among the symptomatic children. The in vitro capacity to attach to oropharyngeal epithelial cells was not increased among the H. influenzae recovered from the eyes. The results question if the majority of conjunctivitis cases were caused by H. influenzae and suggested that eyes were colonized with the nasopharyngeal carrier strain rather than infected by an isolate with special virulence for the eye.

Three cases of Haemophilus influenzae type b (Hib) meningitis in a Swedish day care center prompted the investigation of the nasopharyngeal carriage in attendees of that day care center (I), and among children in another day center (II) in the same city, but without meningitis cases. Because the evaluation of the spread of Haemophilus influenzae (Hi) isolates through a population, such as children in day care centers, requires stable identification markers for the bacteria, this study used multilocus enzyme electrophoresis to separate Hib carried by day care attendees from the disease-associated Hib clone. The three meningitis episodes were caused by the same clone of Hib (ET14). This and other Hib clones occurred in the healthy carriers. The frequency of H. influenzae carriage and composition of the H. influenzae flora differed between the two day care centers. Center I with the meningitis cases had a lower overall frequency of H. influenzae carriage, 11 of 40 (28%) compared with both the control day care center (57%) and previous studies. The main difference between the two day care centers was in the nontypable H. influenzae (HiNT) flora. The frequency of HiNT was higher in the center without Hib disease, and there was a higher degree of sharing of HiNT isolates among the children in Center II. This raised the question of an inverse relationship between carriage of HiNT and Hib infection. The results emphasized the importance of accurate identification of the disease isolate in order to estimate the risk of acquisition and dissemination to secondary cases.

In a kindergarten with 42 children and 17 female staff members, an epidemic of group B streptococcal carriage in the upper respiratory tract occurred. In the middle of February 1978, 6 children and 5 adults carried type I b streptococci in the throat while only 2 of these 11 were carriers 2 weeks later. Only one other streptococcus, belonging to type II, was found in the throat specimens. Five strains other than type I b were found in the urogenital tract of the staff. Three type I b throat carriers were also urogenital carriers of this type. The spread of type I b streptococci could have resulted from co-spreading with other upper respiratory tract pathogens found, including group A streptococci of type 12. Haemophilus influenzae, Branhamella catarrhalis and pneumococci. Estimation of antibodies with radiolabelled protein A indicated an immune response to type I b, but not to types I a, II or III group B streptococci in the staff compared with healthy blood donors.

Haemophilus influenzae meningitis in children 0 to 15 years old was studied retrospectively in a defined region of southwest Sweden from 1971 through 1980; 147 patients with culture-verified H. influenzae meningitis were found. Sixty-seven of them were younger than 18 months and would not have been protected by a purified H. influenzae b polysaccharide vaccine. The age-specific yearly incidence was 27 per 100,000 in the 0- to 4-year age group, 4 per 100,000 in the 5- to 9-year age group and 1 per 100,000 in the 10- to 15-year age group. Predisposing factors were found in only three patients. Two patients died, 3 developed severe neurological sequelae and 19 developed irreversible auditory impairment.

The occurrence of beta-lactamase production in Haemophilus influenzae, Branhamella catarrhalis and Moraxella nonliquefaciens was compared in 191 healthy children attending day nurseries in 2 municipalities differing with regard to the prescription rate of beta-lactam antibiotics. A significantly higher frequency of beta-lactamase production was recorded in M. nonliquefaciens isolated in the municipality with the higher prescription rate. A corresponding difference was not recorded for H. influenzae or B. catarrhalis. Approximately 75% of the nasopharyngeal pathogens H. influenzae, B. catarrhalis and Streptococcus pneumoniae, as well as the commensal M. nonliquefaciens, were eliminated and often replaced by other strains of either species over a period of one month. Although none of the children were on antibiotics a substantial proportion of the acquired strains produced beta-lactamase. This suggested that the carrier rate of beta-lactamase producing strains of the respiratory tract is not only related to the effect of recent antibiotic treatment but also to the prevalence of such strains in the population.

Acute epiglottitis, which is almost exclusively caused by Haemophilus influenzae type b, was studied retrospectively in children 0 to 15 years old in a defined region of southwest Sweden from 1971 through 1980; 211 patients with clinically well-documented acute epiglottitis were found. The age-specific incidence was 14/100,000/year, which was higher than the incidence of H. influenzae meningitis. The median age was 4 years. Because 96% of the patients were older than 18 months, disease in those patients could theoretically have been prevented by the purified H. influenzae polysaccharide vaccine. Only a few patients had underlying diseases. In 186 patients an artificial airway was established. Even though all patients survived without sequelae, the large incidence of the disease emphasizes the importance of H. influenzae in older children.

During two epidemics of influenza A infection in Stockholm 1969-72, 249 cases were selected for a study on the effect of bacterial superinfection. Bacterial involvement was demonstrated through cultures and serologic reactions. The occurrence of C-reactive protein in increased amount in serum was significantly more common in the group which had the strongest indication of bacterial infection. An increased duration of fever, and a higher incidence of pneumonia, leukocytosis and erythrocyte sedimentation rate over 50 mm/l h was also the rule in cases with bacterial involvement. During both epidemics the bacteria most often involved were pneumococci.