Global spatial dynamics and vaccine-induced fitness changes of .

As with other pathogens, competitive interactions between strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.

Reduced Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the Gene Is Geographically Widespread.

Recently, two related strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type , , and clinical strains recovered from intercontinental sources for mutations in We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility to multiple beta-lactam antibiotics.

Comparison of the Impact of Pneumococcal Conjugate Vaccine 10 or Pneumococcal Conjugate Vaccine 13 on Invasive Pneumococcal Disease in Equivalent Populations.

Background: Pneumococcal conjugate vaccine 10 (PCV10) and pneumococcal conjugate vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but direct comparisons of impacts against invasive pneumococcal disease (IPD) in equivalent populations have not been performed. We compared the vaccines (prevaccination 2007-2009 vs postvaccination 2013-2016) in Sweden, where the 21 counties use either PCV10 or PCV13 (introduced 2009-2010).

Methods: All IPD episodes (n = 16992) were recorded in Sweden during 2005-2016.

Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?

Background: Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries.

Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.

The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005-2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated.

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes.

Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study.

Background: Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited.

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O.

Increased incidence of invasive group A streptococcal infections in Sweden, January 2012-February 2013.

The incidence of invasive group A streptococcal infections in Sweden was 6.1 per 100,000 population in 2012, the highest since the disease became notifiable in 2004. Furthermore, January and February 2013 marked a dramatic increase of cases notified, partly explainable by an increase of emm1/T1 isolates, a type previously shown to cause severe invasive disease more often than other types.

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia.

Rationale: Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia.

Objectives: To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia.

Methods: A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden.

Improvement of CRB-65 as a prognostic scoring system in adult patients with bacteraemic pneumococcal pneumonia.

Background: Community-acquired pneumonia (CAP) is the leading cause of hospitalization among infectious diseases, and is mainly caused by Streptococcus pneumoniae. Modifications were tested to improve the accuracy of CRB-65 as a simple but useful bedside scoring system, and to compare it with 3 established severity scoring systems (PSI, CURB-65 and CRB-65) to predict 30-day mortality in bacteraemic pneumococcal CAP.

Methods: A retrospective analysis was performed on data from 375 adult patients with bacteraemic pneumococcal pneumonia.

The epidemiology of pneumococcal infections--the Swedish experience.

Pneumococcal infections are major contributors to morbidity and mortality world-wide and pose a major public health problem. Despite being a devastating pathogen pneumococci are common colonizers of the upper respiratory tract of healthy children. There is a need for more knowledge on the molecular epidemiology, and pathogenesis of pneumococcal infections to be able to find better strategies for prevention and treatment of these common infections.

Severe group A streptococcal infections in Uppsala County, Sweden: clinical and molecular characterization of a case cluster from 2006 to 2007.

This study describes a recent cluster of 30 patients (median age 52 years) with serious group A streptococcal (GAS) infections in Uppsala County, Sweden, from December 2006 to May 2007. Patients hospitalized with a severe GAS infection, i.e.

Bacterial phenotype variants in group B streptococcal toxic shock syndrome.

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively.

Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe.

In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire.

Epidemiology of severe Streptococcus pyogenes disease in Europe.

The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S.

Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation.

Streptococcus pyogenes of the M1 serotype is commonly associated with large outbreaks of invasive streptococcal infections and development of streptococcal toxic shock syndrome (STSS). The pathogenesis behind these infections is believed to involve bacterial superantigens that induce potent inflammatory responses, but the reason why strains of the M1 serotype are over-represented in STSS is still not understood. In the present investigation, we show that a highly purified soluble form of the M1 protein from S.

Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden.

Background: The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population.

Methods: An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Noninvasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison.

A food-borne streptococcal sore throat outbreak in a small community.

Beta-haemolytic group A streptococci (GAS) is a common cause of sore throat, usually spread person-to-person. Outbreaks related to infected food have more seldom been reported. The bacteria may originate from the throat or from wounds on the hands of persons handling the food.

Variations in emm type among group A streptococcal isolates causing invasive or noninvasive infections in a nationwide study.

Since the late 1980s several studies have described the increased incidence and severity of invasive group A streptococcal (GAS) infections. However, most studies on GAS pathogenesis have focused on information obtained during outbreaks. We analyzed isolate distribution and host susceptibility as part of a nationwide prospective surveillance study performed between January 2001 and August 2002.

Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome.

Administration of intravenous polyspecific immunoglobulin G (IVIG) has been proposed as adjunctive therapy for toxic shock syndrome caused by Streptococcus pyogenes or Staphylococcus aureus. We investigated whether superantigen-containing culture supernatants prepared from streptococcal isolates (n=21) and staphylococcal isolates (n=20) from cases of severe sepsis were inhibited to an equal extent by IVIG in proliferation experiments that used human peripheral blood mononuclear cells. All 3 IVIG preparations tested were highly efficient in neutralizing the superantigens, and most supernatants were completely inhibited at concentrations ranging from 0.