Dominance of two genotypes of Bordetella pertussis during a period of increased pertussis activity in Alberta, Canada: January to August 2012.

OBJECTIVES: The purpose of this study was to undertake an epidemiological analysis of an increase in Bordetella pertussis activity during the period January 1 to August 31, 2012 in Alberta, Canada. B. pertussis testing was done using an IS481 real-time PCR assay with PCR-positive and indeterminate specimens cultured and stored for further analysis. METHODS: Laboratory data were linked to Alberta Health (AH) cases that were reported in the Communicable Disease Reporting System (CDRS) to identify case isolates; exclusion criteria were used to avoid biases. Case isolates were analyzed at the National Microbiology Laboratory (NML) by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Pertussis immunization data were extracted from the Alberta Provincial Immunization Repository (Imm/ARI) and linked to the pertussis cases. RESULTS: Using PFGE and MLST, 52 case isolates could be divided into two main sequence type groups: 41 cases belonged to the ST-1 group (ST-1 and the novel ST-19) and 11 cases belonged to the ST-2 group (ST-2 and the novel ST-20). Of the total cases genotyped (N=52), 18 (34.6%) had a history of immunization, 28 (53.8%) were not immunized, and six (11.6%) had an unknown immunization history. Of the total non-immunized cases, 25/28 (89.2%) belonged to the ST-1 group. Furthermore, of the 41 ST-1 group cases, 25 were not immunized compared to only three of the ST-2 group cases (p=0.0004, Fisher's exact test). CONCLUSIONS: This study shows the dominance of two genotypes of B. pertussis in our jurisdiction and indicates less pertussis immunization in individuals infected with the ST-1 group.

Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012.

The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.

Antimicrobial susceptibilities and distribution of sequence types of Neisseria gonorrhoeae isolates in Canada: 2010.

The monitoring of antimicrobial susceptibilities in Neisseria gonorrhoeae isolates and characterization of N. gonorrhoeae multiantigen sequence types (NG-MAST, ST) provide important surveillance data as resistance rates continue to rise. A total of 2970 N. gonorrhoeae isolates were collected by Canadian provincial public health laboratories in 2010, and 1233 were submitted to the National Microbiology Laboratory for testing. The NG-MAST and minimum inhibitory concentration (MIC) by agar dilution were determined for each isolate. Of the 2970 isolates, 25.1% were resistant to penicillin, 34.6% resistant to tetracycline, 31.5% resistant to erythromycin, 35.9% resistant to ciprofloxacin, and 1.2% resistant to azithromycin. Decreased susceptibility to cefixime (MIC ≥ 0.25 mg/L) and ceftriaxone (MIC ≥ 0.125 mg/L) was identified in 3.2% and 7.3% of the isolates, respectively. The most common STs found in Canada were ST1407 (13.3%), ST3150 (11.3%), and ST3158 (9.0%), with 249 different STs identified among the isolates. Within the ST1407 group, 19.5% and 43.3% isolates have decreased susceptibility to cefixime and ceftriaxone, respectively. ST1407, the most prevalent NG-MAST in Canada in 2010, has been associated with high-level ceftriaxone MICs and with cefixime treatment failure cases worldwide. Identification and monitoring of STs and corresponding antimicrobial resistance profiles may be useful in surveillance programs and be used to inform public health actions.

Neisseria gonorrhoeae multiantigen sequence typing is beneficial in further characterizing gonococcal populations in Alberta, Canada.

BACKGROUND: Antimicrobial resistance testing and behavioral data combined with Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) can help to define gonococcal populations and identify, characterize, and compare clusters of infection. METHODS: Antimicrobial resistance testing, using E test, was reviewed for gonococcal isolates in Alberta, Canada, from 2007 to 2011. Antimicrobial resistance testing was conducted on isolates demonstrating antimicrobial resistance and those with cefixime minimum inhibitory concentrations (MICs) of 0.06 µg/mL or greater. Demographic and behavioral information was obtained from provincial surveillance data. NG-MAST typing was conducted on a proportion of isolates. RESULTS: Gonococcal isolates were available for 2250 (26.4%) of 8535 cases of gonorrhea in Alberta from 2007 to 2011. The proportion of cases with decreased susceptibility to cefixime (≥0.06 µg/mL) increased from 0.7% to 2.4% between 2007 and 2009 to a high of 10.1% in 2010 and 8.9% in 2011. Six isolates with cefixime MIC of 0.25 µg/mL were noted: 5 were from men who have sex with men (MSM) and 1 was a pharyngeal isolate from a heterosexual female. Twenty-four (1.1%) isolates were azithromycin resistant (MIC ≥2.0 µg/mL); there were no significant differences between cases resistant or susceptible to azithromycin. NG-MAST of gonococcal isolates in Alberta suggests the entry of multiple strains into the province. Three clusters were identified: Cluster A predominantly in MSM, including sequence type 1407, a ST previously associated with decreased susceptibility to expanded spectrum cephalosporins; Cluster B, a predominantly heterosexual cluster with most cases in Edmonton; and Cluster C among MSM. CONCLUSIONS: Our data highlight the use of NG-MAST in further defining gonococcal populations.

Epidemic of invasive pneumococcal disease, western Canada, 2005-2009.

In Canada before 2005, large outbreaks of pneumococcal disease, including invasive pneumococcal disease caused by serotype 5, were rare. Since then, an epidemic of serotype 5 invasive pneumococcal disease was reported: 52 cases during 2005, 393 during 2006, 457 during 2007, 104 during 2008, and 42 during in 2009. Of these 1,048 cases, 1,043 (99.5%) occurred in the western provinces of Canada. Median patient age was 41 years, and most (659 [59.3%]) patients were male. Most frequently representing serotype 5 cases (compared with a subset of persons with non-serotype 5 cases) were persons who were of First Nations heritage or homeless. Restriction fragment-length polymorphism typing indicated that the epidemic was caused by a single clone, which multilocus sequence typing identified as sequence type 289. Large pneumococcal epidemics might go unrecognized without surveillance programs to document fluctuations in serotype prevalence.

Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus.

Group A Streptococcus (GAS) causes an exceptionally broad range of infections in humans, from relatively mild pharyngitis and skin infections to life-threatening necrotizing fasciitis and toxic shock syndrome. An epidemic of severe invasive human infections caused by type emm59 GAS, heretofore an exceedingly rare cause of disease, spread west to east across Canada over a 3-year period (2006 to 2008). By sequencing the genomes of 601 epidemic, historic, and other emm59 organisms, we discovered that a recently emerged, genetically distinct emm59 clone is responsible for the Canadian epidemic. Using near-real-time genome sequencing, we were able to show spread of the Canadian epidemic clone into the United States. The extensive genome data permitted us to identify patterns of geographic dissemination as well as links between emm59 subclonal lineages that cause infections. Mouse and nonhuman primate models of infection demonstrated that the emerged clone is unusually virulent. Transmission of epidemic emm59 strains may have occurred primarily by skin contact, as suggested by an experimental model of skin transmission. In addition, the emm59 strains had a significantly impaired ability to persist in human saliva and to colonize the oropharynx of mice, and seldom caused human pharyngitis. Our study contributes new information to the rapidly emerging field of molecular pathogenomics of bacterial epidemics and illustrates how full-genome data can be used to precisely illuminate the landscape of strain dissemination during a bacterial epidemic.

International circumpolar surveillance interlaboratory quality control program for serotyping Haemophilus influenzae and serogrouping Neisseria meningitidis, 2005 to 2009.

The International Circumpolar Surveillance (ICS) program was initiated in 1999 to conduct population-based surveillance for invasive pneumococcal disease in select regions of the Arctic. The program was expanded to include the surveillance of invasive diseases caused by Neisseria meningitidis and Haemophilus influenzae. An interlaboratory quality control (QC) program to monitor laboratory proficiencies in the serogrouping of N. meningitidis and serotyping of H. influenzae strains was codeveloped by the Arctic Investigations Program (Anchorage, AK) and the Public Health Agency of Canada National Microbiology Laboratory (Winnipeg, Manitoba, Canada) and introduced into the ICS program in 2005. Other participating laboratories included the Provincial Laboratory for Public Health (Edmonton, Alberta, Canada), Laboratoire Santé Publique du Québec (Sainte-Anne-de-Bellevue, Québec, Canada), and Statens Serum Institut (Copenhagen, Denmark). From 2005 through 2009, 50 isolates (24 N. meningitidis and 26 H. influenzae isolates) were distributed among the five participating laboratories. The overall serogroup concordance for N. meningitidis strains was 92.3% (96/104), without including three isolates that were found to express both serogroup Y and W135 specificities. Concordant results were obtained for serogroups A, B, C, and Y among all laboratories. Discrepancies were observed most frequently for serogroups W135, X, Z, and 29E. The overall serotype concordance for H. influenzae was 98% (125/127 attempts). The two discrepant results involved a serotype c strain and a serotype e strain, and in both cases, the serotypeable H. influenzae isolates were misidentified as being nontypeable. These data demonstrate a high degree of concordance for serogroup and serotype determinations of N. meningitidis and H. influenzae isolates, respectively, among the five laboratories participating in this quality control program.

International external quality assurance for laboratory identification and typing of Streptococcus agalactiae (Group B streptococci).

We report the results from the first international multicenter external quality assessment (EQA) studies for molecular and serological typing of group B streptococcus (GBS) strains as part of DEVANI (Design of a Vaccine against Neonatal Infections), a pan-European program. A questionnaire-based surveillance was undertaken among eight laboratories participating in DEVANI and six laboratories not participating in DEVANI from 13 countries in order to assess their current microbiological procedures for GBS screening, diagnosis, and typing. GBS strains from three EQA distributions were characterized using molecular and serological methods based on GBS capsular polysaccharide typing. Participants were asked to test the first distribution using their current serotyping and genotyping methods. The Strep-B-Latex agglutination method was the most widely used method, with a typeability value of >90%. A multiplex PCR assay for GBS capsular gene typing was also used by 2 of 14 centers, which achieved a typeability value of 93%; this assay detected only 9 of 10 GBS capsular polysaccharide genes. From the second and third EQA studies, standardized protocols were prepared for serological and molecular typing of GBS strains based on the Strep-B-Latex agglutination method and a novel multiplex PCR assay that detected all 10 GBS capsular types (Ia to IX). These standardized protocols are being used by many European laboratories, and as the use of these methods increases, it is imperative to continuously improve and assess laboratory performance and offer training to any laboratories that have technical difficulties.

Epidemic of group A Streptococcus M/emm59 causing invasive disease in Canada.

BACKGROUND: The incidence of invasive group A Streptococcus (GAS) disease can vary over time and geographic region, possibly reflecting the population's susceptibility to particular strains but also variation in the predominant M/emm types. Canadian surveillance documented an epidemic of an uncommon M/emm59 type from 2006 to 2009. METHODS: Invasive GAS isolates are submitted by Public Health Laboratories in Canada to the National Centre for Streptococcus for M/emm typing. Patient age, sex, geographic location, and the anatomical source of isolate are provided with the isolate. When it was recognized that M/emm59 strains were increasing in prevalence, clinical information was collected on M/emm59 cases captured in Alberta and compared with cases of other M/emm types occurring in this province. RESULTS: From January 2006 through December 2009, 539 (13.0%) of 4150 invasive GAS cases were identified as M/emm59: 164 from British Columbia, 146 from Alberta, 62 from Saskatchewan, 82 from Manitoba, 68 from Ontario, 14 from Quebec, 1 from New Brunswick, 1 from Newfoundland, 1 from Yukon, and 1 from Nunavut. The predominant clinical presentation was bacteremia (45.0%) followed by cellulitis (41.4%). Compared with concurrent cases of invasive GAS disease caused by all other M/emm types, identified risk factors for M/emm59 disease were alcohol abuse (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-3.8), homelessness (OR, 2.0; 95% CI, 1.2-3.4), hepatitis C virus infection (OR, 2.0; 95% CI, 1.1-3.5), and illicit drug use (OR, 1.7; 95% CI, 1.0-3.0). CONCLUSIONS: Western Canada has witnessed the rapid emergence of a rare GAS strain causing invasive disease predominately in a select population of disadvantaged persons.

Antimicrobial resistance in gonorrhea: the influence of epidemiologic and laboratory surveillance data on treatment guidelines: Alberta, Canada 2001-2007.

OBJECTIVES: To describe the impact of surveillance for antimicrobial resistance (AMR) in Neisseria gonorrhoeae over a 7-year period on treatment guidelines in Alberta, Canada. METHODS: AMR testing data from gonorrhea cases were combined with demographic and risk behavior information collected through surveillance to describe trends and sequential changes to treatment guidelines. RESULTS: Ciprofloxacin resistant gonorrhea (CRG) cultures rose from 1.4% in 2001 to 27.7% in 2007. Of 200 CRG cases, 90% were men, 77% white, median age 29 years (interquartile range: 23-29 years) and 60% were men who have sex with men (MSM). In 2005, only 1 of 28 cases did not fit into travel or MSM categories and treatment guidelines were changed to recommend oral cefixime as the preferred agent in MSM or those with a travel history. Continuous rise in CRG together with locally acquired cases among heterosexuals resulted in ciprofloxacin being removed as a recommended agent for gonorrhea in 2007. CONCLUSIONS: Our data underscores the importance of surveillance in monitoring trends in AMR in gonorrhea so that timely changes to treatment recommendations can be made in response to changing epidemiology.

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae pre- and post-seven valent pneumococcal conjugate vaccine introduction in Alberta, Canada, 2000-2006.

Alberta, Canada introduced the Streptococcus pneumoniae seven valent conjugate vaccine (PCV7) program for children less than 2 years of age in September 2002. We determined the rates of invasive pneumococcal disease in Alberta, Canada 2 years pre- and 4 years post-PCV7 introduction (2000-2006) as well as the rates of antibiotic resistance and serotype distribution in this same time period. Overall, PCV7 serotypes decreased 61% from 2000 to 2006. The greatest decrease in incidence of invasive pneumococcal disease occurred in children less than 2 years of age declining from a high of 96.7/100,000 (2000) to 25.8/100,000 (2006) (P<0.0001). Non-susceptibility of S. pneumoniae isolates to penicillin dropped significantly from 14% in 2000 to 4.6% in 2006 (P<0.0001). Non-susceptible erythromycin isolates also decreased from 8.8% (2000) to 5.8% (2006) (P=0.13). The introduction of PCV7 in Alberta, Canada has decreased the incidence of invasive pneumococcal disease in Alberta as well as resulting in a decrease in antibiotic resistance over this same time frame, principally for penicillin resistance.

Utility of the pneumoslide test in identification of Streptococcus pneumoniae in blood cultures and its relation to capsular serotype.

The performance of the Pneumoslide test for rapid identification of Streptococcus pneumoniae was evaluated when used directly on positive blood culture specimens. The sensitivity was 75.3%, and the specificity was 98.6%. Pneumoslide test performance accuracy varied depending on the pneumococcal serotype.

Epidemiology of invasive pneumococcal disease in BC during the introduction of conjugated pneumococcal vaccine.

OBJECTIVES: Antimicrobial resistance in Streptococcus pneumoniae has increased in recent decades. We linked two surveillance programs to evaluate trends in incidence, serotype distribution, and antimicrobial resistance in invasive pneumococcal disease (IPD) since the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in BC in 2003. METHODS: IPD case reports for BC from 2002-2005 from the BC Centre for Disease Control were linked to serotype and antimicrobial susceptibility results from the National Centre for Streptococcus (NCS). RESULTS: There was a significant decrease in IPD incidence in children <5 from 54/100,000 in 2002 to 16/100,000 population in 2005 (70% decrease, p < 0.001). The most dramatic decline was in children aged 1 year, where the rate fell from 135/100,000 to 15/100,000 (89% decrease, p for trend <0.001). Overall, 728/1288 (56.5%) reported cases of IPD were referred to NCS. For all matched cases, the proportion of isolates of PCV7 preventable serotypes decreased from 68.9% to 43.8% (p for trend <0.001) between 2002 and 2005. In children <2 years, this proportion decreased from 83.0% (39/47 cases) to 16.7% (1/6 cases) (p = 0.006). The prevalence of non-susceptible isolates was highest for trimethoprim-sulfamethoxazole (15.3%, 111/725 tested), penicillin (9.1%, 66/728), and erythromycin (9.1%, 66/727). 10.3% (75/728) were non-susceptible to > or =2 classes of antimicrobials. Children <15 years of age had the highest proportion of non-susceptible isolates. DISCUSSION: The incidence of IPD in children has decreased significantly since the introduction of PCV7. Comprehensive serotype and antimicrobial susceptibility can aid in evaluating the impact of immunization programs.

International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005.

The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.

Invasive bacterial diseases in northern Canada.

International Circumpolar Surveillance (ICS) is a population-based invasive bacterial disease surveillance network. Participating Canadian regions include Yukon, Northwest Territories, Nunavut, and northern regions of Québec and Labrador (total population 132,956, 59% aboriginal). Clinical and demographic information were collected by using standardized surveillance forms. Bacterial isolates were forwarded to reference laboratories for confirmation and serotyping. After pneumococcal conjugate vaccine introduction, crude annual incidence rates of invasive Streptococcus pneumoniae decreased from 34.0/100,000 population (1999-2002) to 23.6/100,000 population (2003-2005); substantial reductions were shown among aboriginals. However, incidence rates of S. pneumoniae, Haemophilus influenzae, and group A streptococci were higher in aboriginal populations than in non-aboriginal populations. H. influenzae type b was rare; 52% of all H. influenzae cases were caused by type a. Data collected by ICS contribute to the understanding of the epidemiology of invasive bacterial diseases among northern populations, which assists in formulation of prevention and control strategies, including immunization recommendations.

Epidemiology of Haemophilus influenzae serotype a, North American Arctic, 2000-2005.

Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of invasive H. influenzae disease among indigenous people of the North American Arctic were among the highest in the world. Routine vaccination reduced rates to low levels; however, serotype replacement with non-type b strains may result in a reemergence of invasive disease in children. We reviewed population-based data on invasive H. influenzae in Alaska and northern Canada from 2000-2005; 138 cases were reported. Among 88 typeable isolates, 42 (48%) were H. influenzae type a (Hia); 35 (83%) occurred in indigenous peoples. Among Hia patients, median age was 1.1 years; 62% were male; 1 adult died. Common clinical manifestations included meningitis, pneumonia, and septic arthritis. Overall annual incidence was 0.9 cases per 100,000 population. Incidence among indigenous children <2 years of age in Alaska and northern Canada was 21 and 102, respectively. Serotype a is now the most common H. influenzae serotype in the North American Arctic; the highest rates are among indigenous children.

Evolution of an international external quality assurance model to support laboratory investigation of Streptococcus pneumoniae, developed for the SIREVA project in Latin America, from 1993 to 2005.

In 1993 the Pan American Health Organization initiated a laboratory-based surveillance system, called the SIREVA project, to learn about Streptococcus pneumoniae invasive disease in Latin American children. In 1994, National Laboratories in six countries were trained to perform serotyping and antibiotic susceptibility testing using broth microdilution to determine the MIC for specified antibiotics. An international External Quality Assurance (EQA) program was developed to monitor and support ongoing laboratory performance. The EQA program was coordinated by the National Centre for Streptococcus (NCS), Edmonton, Canada, and included external proficiency testing (EPT) and a validation process requiring regular submission of a sample of isolates from each laboratory to the NCS for verification of the serotype and MIC. In 1999, the EQA program was decentralized to use three of the original laboratories as regional quality control centers to address operational concerns and to accommodate the growth of the laboratory network to more than 20 countries including the Caribbean region. The overall EPT serotyping accuracies for phase I (1993 to 1998) and phase II (1999 to 2005) were 88.0 and 93.8%, respectively; the MIC correlations within +/-1 log(2) dilution of the expected result were 83.0 and 91.0% and the interpretive category agreements were 89.1 and 95.3%. Overall, the validation process serotyping accuracies for phases I and II were 81.9 and 88.1%, respectively, 80.4 and 90.5% for MIC agreement, and 85.8 and 94.3% for category agreement. These results indicate a high level of testing accuracy in participating National Laboratories and a sustained increase in EQA participation in Latin America and the Caribbean.

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.

International quality assurance study for characterization of Streptococcus pyogenes.

Surveillance of group A streptococcal (GAS) infections was undertaken as a major component of the European Commission-funded project on severe GAS disease in Europe (strep-EURO). One aim of strep-EURO was to improve the quality of GAS characterization by standardization of methods. An external quality assurance study (EQA) was therefore carried out to evaluate current global performance. Eleven strep-EURO and seven other streptococcal reference centers received a panel of 20 coded GAS isolates for typing. Conventional phenotypic typing (based on cell surface T and M protein antigens and opacity factor [OF] production) and molecular methods (emm gene typing) were used either as single or combined approaches to GAS typing. T typing was performed by 16 centers; 12 centers found one or more of the 20 strains nontypeable (typeability, 89%), and 11 centers reported at least one incorrect result (concordance, 93%). The 10 centers that tested for OF production achieved 96% concordance. Limited availability of antisera resulted in poor typeability values from the four centers that performed phenotypic M typing (41%), three of which also performed anti-OF typing (typeability, 63%); however, concordance was high for both M (100%) and anti-OF (94%) typing. In contrast, the 15 centers that performed emm gene sequencing achieved excellent typeability (97%) and concordance (98%), although comparison of the performance between centers yielded typeability rates from 65 to 100% and concordance values from 83 to 100%. With the rapid expansion and use of molecular genotypic methods to characterize GAS, continuation of EQA is essential in order to achieve international standardization and comparison of type distributions.

Invasive group A streptococcal disease in Alberta, Canada (2000 to 2002).

Invasive group A streptococcal (iGAS) disease was placed under surveillance in Alberta in August 1999. The purpose of this study was to determine the incidence rates of iGAS infections throughout Alberta over a 3-year period (2000 to 2002) and to better understand the epidemiology of iGAS in this province. There were a total of 441 cases of invasive GAS disease over the 3 years examined (average population over 3 years, 3,055,765) and 47 deaths. The incidence in Alberta was 5.0 (2000), 5.7 (2001), and 3.8 (2002) per 100,000. The two main metropolitan regions (Edmonton and Calgary) had the majority of iGAS disease cases (305 cases), producing incidence rates of 4.8 (Edmonton) and 6.9 (Calgary) in 2000, 6.9 (Edmonton) and 6.6 (Calgary) in 2001, and 4.1 (Edmonton) and 3.9 (Calgary) in 2002, as well as deaths attributable to GAS (31 deaths). The three most prevalent M types were M1 (71 cases), M3 (52 cases), and MPT2967 (44 cases). With respect to age, the highest incidence rates occurred in those less than 1 year old (11.7 per 100,000) and those 65 years or older (11.5 per 100,000). Varicella virus infection preceded iGAS disease in 25% of children 8 years of age and under. A seasonal association was observed during the 3 years studied, with the highest number of cases occurring in the winter months and the lowest occurring during the summer months. The data for years 2000 and 2001 show that the metropolitan regions of Alberta experienced some of the highest incidence rates reported in North America in the past decade.