Greater time spent with HbA1c less than 7.0% with oral semaglutide versus oral comparators: An exploratory analysis of the PIONEER studies.

AIM: To assess how long participants with type 2 diabetes spent with HbA1c less than 7.0% and how likely they were to maintain this target with oral semaglutide 7 mg versus sitagliptin 100 mg or oral semaglutide 14 mg versus empagliflozin 25 mg, sitagliptin 100 mg or subcutaneous liraglutide 1.8 mg. MATERIALS AND METHODS: Analyses used on-treatment data without rescue medication for all randomized participants (semaglutide [approved maintenance doses], n = 1880; comparators [not including placebo], n = 1412). Duration of time with HbA1c less than 7.0% was calculated using an HbA1c time curve. A binary endpoint of achieving HbA1c less than 7.0% at weeks 26 (week 24 for PIONEER 7) and 52 of each trial (and week 78 for PIONEER 3) was analysed. RESULTS: Mean duration of time with HbA1c less than 7.0% was greater with oral semaglutide 7 mg versus sitagliptin in PIONEER 3 (27 vs. 22 weeks) and with oral semaglutide 14 mg versus empagliflozin and sitagliptin (27-34 vs. 19 vs. 22 weeks, respectively), and similar versus subcutaneous liraglutide. A greater proportion of participants achieved and maintained HbA1c less than 7.0% for more than 75% of the trial with oral semaglutide 14 mg versus oral comparators. The odds of achieving HbA1c less than 7.0% at weeks 24/26 and 52/78 were significantly greater with oral semaglutide 14 mg versus oral comparators or subcutaneous liraglutide, and with oral semaglutide 7 mg versus sitagliptin. CONCLUSIONS: Oral semaglutide 7 and 14 mg resulted in greater time spent with HbA1c less than 7.0%, and a greater likelihood of achieving and maintaining HbA1c less than 7.0% versus oral comparators.

CAPTURE: a multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries.

BACKGROUND: There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials. METHODS: Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters. RESULTS: The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6-17.9 years) and glycated hemoglobin 7.3% (6.6-8.4%) [56 mmol/mol (49-68 mmol/mol)]. Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval [CI] 32.7-36.8) and 31.8% (95% CI 29.7-33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively. CONCLUSIONS: In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).

Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i.

AIMS: The LIRA-ADD2SGLT2i trial demonstrated that liraglutide + sodium-glucose cotransporter-2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post-hoc analysis assessed whether baseline characteristics influenced these findings. MATERIALS AND METHODS: LIRA-ADD2SGLT2i (NCT02964247) was a placebo-controlled, double-blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre-trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand. RESULTS: Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%-<7.6%; 7.6%-8.1%; ≥8.2%-9.5%) and glycaemic control at week 26 (p[interaction]  = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [-0.20% (-0.59, 0.19); -0.68% (-1.03, -0.33); -0.98% (-1.33, -0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA-IR or SGLT2i use duration (p[interaction] > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p[interaction] > .05, all). CONCLUSION: For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA-IR and SGLT2i use duration.

Diabetes-Related Effectiveness and Cost of Liraglutide or Insulin in German Patients with Type 2 Diabetes: A 5-Year Retrospective Claims Analysis.

INTRODUCTION: Liraglutide is a glucagon-like peptide-1 analogue used to treat type 2 diabetes mellitus (T2DM). To date, limited long-term data (> 2 years) exist comparing real-world diabetes-related effectiveness and costs for liraglutide versus insulin treatment. METHODS: This retrospective claims data analysis covered the period from 1 January 2010 to 31 December 2017 and included continuously insured patients with T2DM who initiated insulin or liraglutide and had 3.5 or 5 years' follow-up data, identified using the German AOK PLUS dataset. Propensity score matching (PSM) was used to adjust for patient characteristics. RESULTS: After PSM, there were 825 and 436 patients in the liraglutide and insulin groups at 3.5 and 5 years' follow-up, respectively. Baseline characteristics were similar between compared cohorts. The respective change from baseline to follow-up in mean glycated haemoglobin for liraglutide and insulin patients was - 0.88% and - 0.81% (p > 0.100) after 3.5 years and - 1.15%/ - 1.02% (p > 0.100) after 5 years. Mean respective changes in body mass index (kg/m2) were - 1.21/+ 1.14 (p < 0.001) after 3.5 years and - 1.29/+ 1.13 after 5 years (p < 0.001). Liraglutide- versus insulin-treated patients were less likely to have an early T2DM-related hospitalisation (3.5-year hazard ratio [HR]: 0.414 [95% confidence interval (CI) 0.263-0.651]; 5-year HR: 0.448 [95% CI 0.286-0.701]). At 5 years' follow-up, there was no statistically significant difference in total direct costs between treatment groups (cost ratio: 1.069 [95% CI 0.98-1.13]; p > 0.100). CONCLUSION: The clinical effectiveness of liraglutide is maintained long term (up to 5 years). Liraglutide treatment is not associated with higher total direct healthcare costs.

Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial.

AIM: To compare the effect of liraglutide or placebo added on to sodium-glucose co-transporter-2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%-9.5% and body mass index [BMI] ≥ 20 kg/m2 ) were randomized 2:1 to add-on liraglutide 1.8 mg/day or placebo in this parallel, double-blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed. RESULTS: Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were - 0.98% and - 0.30%, respectively (estimated treatment difference [ETD]: -0.68% [95% CI: -0.89, -0.48]; P < 0.001). Mean body weight changes from baseline were - 2.81 versus -1.99 kg, respectively (ETD: -0.82 kg [95% CI: -1.73, 0.09]; P = 0.077); 51.8% of liraglutide-treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 [95% CI: 2.67, 9.87]; P < 0.001). More patients treated with liraglutide reported ≥1 treatment-emergent adverse events (66.3%) versus placebo (47.0%). CONCLUSIONS: Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.

Is there an association between liraglutide use and female breast cancer in a real-world setting?

BACKGROUND: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza®) and more recently at 3.0 mg/day for weight management (Saxenda®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting. PATIENTS AND METHODS: Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010-2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two "all comparators" groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed. RESULTS: Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67-1.22) for both the "all comparator" and "all comparator except exenatide" cohorts to 1.46 (95% CI: 0.96-2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC. CONCLUSION: Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk.

Competition between Streptococcus pneumoniae strains: implications for vaccine-induced replacement in colonization and disease.

BACKGROUND: Vaccine-induced replacement by nonvaccine serotypes in pneumococcal colonization and disease poses a threat to the long-term effectiveness of pneumococcal vaccination. One of the main drivers for serotype replacement is likely to be the competitive interactions between pneumococcal serotypes. METHODS: We used longitudinal datasets of pneumococcal colonization among infants (American Indian and The Gambia) and toddlers (Denmark) to study the strength and mechanism of competition between pneumococcal serotypes. We characterized the strength of competition as the relative reduction in the expected time spent colonized with two serotypes (double colonization) as compared with colonization with no competition. We also assessed the mechanism of competition, that is, whether reduction in double colonization is due to reduced rate of acquisition or enhanced clearance of colonization. The three datasets were analyzed assuming both perfect (100%) and imperfect (50%) sensitivity in detection of double colonization. RESULTS: Each dataset showed strong between-serotype competition, and competition in acquisition was clearly identified. These findings remained in the secondary analysis assuming only 50% sensitivity to detect double colonization. Inferences about enhanced clearance due to competition were susceptible to the assumed sensitivity of detection. CONCLUSIONS: Strong competition between pneumococcal serotypes can explain the prompt replacement by the nonvaccine serotypes in vaccinated persons and populations. The main mechanism of between-serotype interaction was identified as competition in acquisition, which suggests that replacement in pneumococcal disease depends largely on propensities of the replacing serotypes to cause disease through acquisition of colonization.

A Pneumococcal Carriage Study in Danish Pre-school Children before the Introduction of Pneumococcal Conjugate Vaccination.

We present data on pneumococcal carriage before the introduction of the heptavalent-pneumococcal conjugated vaccine (PCV7) in Denmark. In the pre-PCV7 period, the incidence of invasive pneumococcal disease (IPD) among children younger than 5 years was approximately 25 per 100.000 population, with the highest incidence rates observed in children younger than 2 years of age. The study included 437 children aged 12-72 months attending day care centres (DCC) and was conducted during 48 months. In total, 56% (n=247) of children were pneumococcal carriers with the highest prevalence in children aged 12-23 months (69%), the proportion significantly declining with increasing age. PCV7 serotypes accounted for 33%, PCV10 for 34%, and PCV13 for 57% of all carried isolates. The proportion of serotypes included in the three conjugate vaccines was higher among IPD isolates compared to carrier isolates (range 35- 90%). We found that the frequency of carriage was high among Danish pre-school children attending DCC and serotypes were not frequently covered by PCV7 in the pre-PCV7 period.

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine.

AIM: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007. METHODS: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996-2007, were retrospectively reviewed. RESULTS: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children <16 years, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known risk factors. The Streptococcus pneumoniae serotype was available for 81 cases. Seventy-five percent of the IPD cases in children aged <2 years were caused by one of the serotypes contained within PCV7, compared to only 24% in children >/=2 years. CONCLUSION: Our data indicate that an estimated 75% of all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination.

An easy method for detection of nasopharyngeal carriage of multiple Streptococcus pneumoniae serotypes.

In this paper, a simplified method for detection of pneumococcal carriage and for revealing the presence of several serotypes in a nasopharyngeal sample is evaluated. Enrichment broth was used for transportation and for the initial culturing of samples. All specimens were examined directly by the capsular reaction test for the presence of any of the 91 known pneumococcal serotypes. Sub-culturing on blood agar was used for isolation of the pneumococcal strains detected in the primary broth culture. A total of 693 nasopharyngeal swabs were obtained among children, their parents and employees in day care centres. Pneumococci were observed in 363 samples and 36 of these (9.9%) contained more than one serotype (multiple carriages). Two persons carried 3 different serotypes simultaneously. A significant increase in the positive sampling rate (5.8%) was achieved by using the simplified method compared to conventional streaking of the swabs directly on blood agar (p<0.0001).

Genetic relatedness of the Streptococcus pneumoniae capsular biosynthetic loci.

Streptococcus pneumoniae (the pneumococcus) produces 1 of 91 capsular polysaccharides (CPS) that define the serotype. The cps loci of 88 pneumococcal serotypes whose CPS is synthesized by the Wzy-dependent pathway were compared with each other and with additional streptococcal polysaccharide biosynthetic loci and were clustered according to the proportion of shared homology groups (HGs), weighted for the sequence similarities between the genes encoding the shared HGs. The cps loci of the 88 pneumococcal serotypes were distributed into eight major clusters and 21 subclusters. All serotypes within the same serogroup fell into the same major cluster, but in six cases, serotypes within the same serogroup were in different subclusters and, conversely, nine subclusters included completely different serotypes. The closely related cps loci within a subcluster were compared to the known CPS structures to relate gene content to structure. The Streptococcus oralis and Streptococcus mitis polysaccharide biosynthetic loci clustered within the pneumococcal cps loci and were in a subcluster that also included the cps locus of pneumococcal serotype 21, whereas the Streptococcus agalactiae cps loci formed a single cluster that was not closely related to any of the pneumococcal cps clusters.

Bordetella pertussis strains circulating in Europe in 1999 to 2004 as determined by pulsed-field gel electrophoresis.

Clinical isolates of Bordetella pertussis collected during the year 2004 (n = 153) in eight European countries, Denmark, Finland, France, Germany, The Netherlands, Poland, Sweden, and United Kingdom, were analyzed by pulsed-field gel electrophoresis (PFGE), and their PFGE profiles were compared with those of isolates collected in 1999 (n = 102). The 255 isolates produced 59 distinct PFGE profiles. Among the 153 isolates from 2004, 36 profiles were found, while within the 102 isolates from 1999, 33 profiles were detected. One PFGE profile, BpSR11, was dominant (30% to 50%) in all countries except Denmark (10%) and Poland (0%). In comparison with 1999, there was an increase in BpSR11 prevalence in Finland in 2004 from 5% to 40%, coinciding with a major incidence peak. Some other PFGE profiles seemed to be associated with limited dissemination. Poland was the only country in which the most common actual European PFGE profiles were not found. In a dendrogram analysis, all common PFGE profiles were identified within PFGE group IV, and BpSR11 clustered together with PFGE subgroup IVbeta. Compared to the 1999 isolates, PFGE group V representative for pertactin variant prn3 strains had disappeared, and a new cluster was seen. In conclusion, some PFGE profiles, such as BpSR11, evidently have a higher capacity to spread, suggesting increased fitness to the present immunological environment. It is therefore of major interest to continue with surveillance programs of B. pertussis isolates, as both waning vaccine-derived immunity and strain variation may play a role in the persistence of pertussis.

A comparison of antibiotic use in children between Canada and Denmark.

BACKGROUND: High rates of antibiotic prescribing in children lead to antibiotic resistance in the community. Surveillance on utilization rates and comparisons with other jurisdictions are methods for benchmarking. Surveillance on antibiotic use is well established in Europe, including Denmark, but until recently, similar data from Canada were lacking. OBJECTIVE: To compare pediatric antibiotic prescribing rates in British Columbia, Canada, with those in Denmark. METHODS: Population-based data on antibiotic prescriptions from British Columbia and Denmark were obtained from 1999 to 2003 for children less than 15 years of age. Annual trends in prescription rates per 1000 children were analyzed by using generalized linear models for all children less than 15 years of age; they were stratified by age group (0-4, 5-9, 10-14 y) for all antibiotics. Class-specific trends were also evaluated for penicillins, cephalosporins, macrolides, sulfonamides and trimethoprim, tetracyclines, and fluoroquinolones. RESULTS: From 1999 to 2003, the overall British Columbia prescription rate was significantly higher than that of Denmark (p < 0.0001) at all age stratifications. In 2003, the British Columbia prescription rate was twice that of Denmark, at 608 versus 385 prescriptions per 1000 children, respectively. In both jurisdictions, the majority of antibiotics used were penicillins (Anatomical Therapeutic Chemical class J01C). However, in British Columbia, most penicillins used were extended-spectrum (83% in 2003); in Denmark, 34% of penicillins used in 2003 were extended-spectrum and 56% were beta-lactamase sensitive. In British Columbia, use of penicillins (-4.5%), cephalosporins (-5.5%), trimethoprim/sulfamethoxazole (-36%), and tetracycline (-1.6%) decreased over time, whereas in Denmark, use of penicillins increased by 11% over time and non-penicillin antibiotics remained stable. A significant increase in macrolide consumption was seen in British Columbia due to use of clarithromycin and azithromycin; in contrast, macrolide consumption declined in Denmark. CONCLUSIONS: Compared with Denmark, the antibiotic prescription rate for children is substantially higher in British Columbia. In addition, there has been a significant increase in the use of macrolides, especially the second-generation agents, in British Columbia compared with the use in Denmark. Further studies are required to delineate reasons for antibiotic prescribing patterns in these 2 jurisdictions.

Perinatal and crowding-related risk factors for invasive pneumococcal disease in infants and young children: a population-based case-control study.

BACKGROUND: Denmark's systems of registry-based data offer a unique opportunity to examine, on a population basis, risk factors for invasive pneumococcal disease (IPD) relating to perinatal and crowding exposures among children. The main objective of this study was to identify the role of familial and day care factors in the risk of IPD among unvaccinated infants and children. METHODS: A total of 1381 children aged 0-5 years old who experienced IPD were identified from a national surveillance program of IPD in Denmark. Risk factors were assessed in a matched, nested, case-control study that assigned 10 population control subjects to every case patient. Exposure information was obtained from several population-based, person-identifiable Danish registries. RESULTS: Preterm birth and low birth weight significantly increased the risk of IPD among infants. In infants 0-5 months of age, the risk of IPD was high among infants who had older siblings, compared with infants of the same age who had no older siblings (adjusted rate ratio [aRR], 3.38; 95% confidence interval, 2.11-5.42), whereas the aRR was low (aRR, 0.56; 95% confidence interval, 0.47-0.65) in children aged 6-23 months. Day care attendance, compared with home care, increased the aRR of IPD 0-2 months after enrollment in a day care program (aRR, 2.28; 95% confidence interval, 1.73-3.00), whereas the aRR was 0.70; (95% confidence interval, 0.46-1.06) > or = 6 months after enrollment in children aged 6-23 months. CONCLUSIONS: During infancy (age, 0-6 months), risk of IPD is associated with low birth weight, presumably because of lower levels of passively acquired maternal antibody. During early childhood, exposure to other young children (either siblings or through day care attendance) is clearly associated with IPD, but natural exposure appears to occur rapidly and confer durable immunity.

Serotypes of Streptococcus pneumoniae isolated from blood and cerebrospinal fluid related to vaccine serotypes and to clinical characteristics.

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.

Validation of a multiplex pneumococcal serotyping assay with clinical samples.

We have recently developed a rapid pneumococcal serotyping method called "multibead assay" (J. Yu et al., J. Clin. Microbiol. 43:156-162, 2005) based on a multiplexed immunoassay for capsular polysaccharides in lysates of pneumococcal cultures. The multibead assay can identify 36 serotypes (1, 2, 3, 4, 5, 6A, 6B, 7A/7F, 8, 9L/9N, 9V, 10A/10B/39/33C, 11A/11D/11F, 12A/12B/12F, 14, 15B/5C, 17F, 18C, 19A, 19F, 20, 22A/22F, 23F, and 33A/33F). More than 90% of the U.S. isolates express one of these serotypes (J. B. Robbins et al., J. Infect. Dis. 148:1136-1159, 1983). To validate the new assay, we examined 495 clinical isolates of pneumococci obtained in Brazil, Denmark, and Mexico. Pneumococci were serotyped by the Neufeld test in their countries of origin, and lysates of each strain were coded and mailed to the United States for the multibead assay at ambient temperature without any thermal protection. After breaking the code, 54 discrepancies (11% of samples) were noted, but 46 were due to nonreproducible technical problems or insufficient growth of the pneumococci. All of the isolates grew well for a second test, and therefore, the culture medium used for the multibead assay is adequate. The discrepancies persisted for eight isolates, involving the 6A, 11A, and 18C serotypes. Additional studies of the eight isolates showed that the discrepancies were due to differences in the reagents used in the multibead or Neufeld tests for these three serotypes. For instance, five isolates were typed as 6A with the Neufeld test but as nontypeable by the multibead assay. Selection of another new monoclonal antibody (Hyp6AG1) for the multibead assay resulted in all five discrepant isolates typing as 6A. This finding indicates the validity of the multibead assay and emphasizes the need to validate any new pneumococcal serotyping assay with a large number of clinical isolates from different locations. It also suggests the presence of serological subtypes among isolates expressing the 6A serotype.

Emergence of invasive serotype VIII group B streptococcal infections in Denmark.

Serotype VIII group B streptococcus has only rarely been described outside Japan. The Streptococcus Unit, Statens Serum Institut, performed national surveillance of invasive group B streptococcal (GBS) diseases in Denmark in 1999 to 2002 and identified seven clinical GBS isolates of serotype VIII in blood from seven patients admitted to different hospitals.

Community outbreak of perianal group A streptococcal infection in Denmark.

BACKGROUND: Perianal group A streptococcal infection (PASI) occurs primarily in children. There is limited information on the incidence, transmission and treatment of PASI. We report a cluster of cases connected to a Danish kindergarten and observations of the incidence of PASI in the local population. SETTING: A Danish rural community with 1765 children 15 years and younger registered with two general practice clinics. METHODS: After being alerted of a possible cluster of PASI cases, all isolates of group A beta-hemolytic streptococci were collected and subjected to T typing and pulsed field gel electrophoresis (PFGE) if grown from either a rectal swab or an accompanying throat swab obtained in the offices of local general practitioners during the ensuing 4-month period. Clinical data were obtained from the files of the local general practitioners. RESULTS: Twelve cases of PASI were caused by group A beta-hemolytic streptococci T type 28 with an identical PFGE profile: 6 of the cases were in children attending the same kindergarten, 4 were connected otherwise to the cluster and 2 cases seemed to be unrelated. Five cases of PASI with different T types and PFGE profiles were diagnosed during the same period giving an estimated annual incidence of 2 to 7 per 1000 children. Penicillin V was ineffective in 3 cases, and no recurrence was seen after change of the treatment to oral clarithromycin. CONCLUSIONS: A clone of T type 28 seemed to be the cause of the largest cluster of PASI cases described thus far. Clarithromycin was effective as second line treatment. An estimated annual baseline incidence of 2 to 7 per 1000 in the local population indicates that PASI may not be as rare as previously estimated.