Marguerite Lovgren

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999

BACKGROUND Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.Background. Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. Methods. The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. Results. By June, 1999, 4105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. Conclusion. These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

Invasive Streptococcus pneumoniae Infection in Latin American Children: Results of the Pan American Health Organization Surveillance Study

Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae promise to be an effective public health intervention for children, especially in an era of increasing antimicrobial resistance. To characterize the distribution of capsular types in Latin America, surveillance for invasive pneumococcal infection in children < or = 5 years of age was done in six countries between February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were from children with pneumonia, and 52% were isolated from blood. The 15 most common of the capsular types prevalent throughout the region accounted for 87.7% of all isolates. Overall, 24.9% of isolates had diminished susceptibility to penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance. Three customized vaccine formulas containing 7, 12, and 15 capsular types were found to have regional coverages of 72%, 85%, and 88%, respectively. This study emphasizes the need for local surveillance for invasive pneumococcal disease prior to the development and evaluation of protein-polysaccharide conjugate vaccines for children.

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.

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

Serotype a is now the most common seen in the North American Arctic; highest rates occur in indigenous children.

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.

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.

Enterococcus gilvus sp. nov. and Enterococcus pallens sp. nov. Isolated from Human Clinical Specimens

ABSTRACT Light yellow-pigmented (strain PQ1) and yellow-pigmented (strain PQ2), gram-positive, non-spore-forming, nonmotile bacteria consisting of pairs or chains of cocci were isolated from the bile of a patient with cholecystitis (PQ1) and the peritoneal dialysate of another patient with peritonitis (PQ2). Morphologically and biochemically, the organisms phenotypically belonged to the genus Enterococcus. Whole-cell protein (WCP) analysis and sequence analysis of a segment of the 16S rRNA gene suggested that they are new species within the genus Enterococcus. PQ1 and PQ2 displayed less than 70% identities to other enterococcal species by WCP analysis. Sequence analysis showed that PQ1 shared the highest level of sequence similarity with Enterococcus raffinosus and E. malodoratus (sequence similarities of 99.8% to these two species). Sequence analysis of PQ2 showed that it had the highest degrees of sequence identity with the group I enterococci E. malodoratus (98.7%), E. raffinosus (98.6%), E. avium (98.6%), and E. pseudoavium (98.6%). PQ1 and PQ2 can be differentiated from the other Enterococcus spp. in groups II, III, IV, and V by their phenotypic characteristics: PQ1 and PQ2 produce acid from mannitol and sorbose and do not hydrolyze arginine, placing them in group I. The yellow pigmentation differentiates these strains from the other group I enterococci. PQ1 and PQ2 can be differentiated from each other since PQ1 does not produce acid from arabinose, whereas PQ2 does. Also, PQ1 is Enterococcus Accuprobe assay positive and pyrrolidonyl-β-naphthylamide hydrolysis positive, whereas PQ2 is negative by these assays. The name Enterococcus gilvus sp. nov. is proposed for strain PQ1, and the name Enterococcus pallens sp. nov. is proposed for strain PQ2. Type strains have been deposited in culture collections as E. gilvus ATCC BAA-350 (CCUG 45553) and E. pallens ATCC BAA-351 (CCUG 45554).

International circumpolar surveillance system for invasive pneumococcal disease, 1999-2005

Disease rates are high among indigenous persons in Arctic countries, and PCV7 has resulted in decreased rates in North American children.

Invasive Group A Streptococcal Disease in Alberta, Canada (2000 to 2002)

ABSTRACT 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.

International External Quality Assurance for Laboratory Identification and Typing of Streptococcus agalactiae (Group B Streptococci)

ABSTRACT 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.