Androulla Efstratiou - Academia.edu (original) (raw)

Papers by Androulla Efstratiou

Research paper thumbnail of Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010

Eurosurveillance, 2010

We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterina... more We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified.

Research paper thumbnail of Invasive Group A<i>Streptococcus</i>Infection among Children, Rural Kenya

Emerging Infectious Diseases, Feb 1, 2016

To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the s... more To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998-2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person-years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type-specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence.

Research paper thumbnail of Characterization of Toxigenic <i>Corynebacterium ulcerans</i> Strains Isolated from Humans and Domestic Cats in the United Kingdom

Journal of Clinical Microbiology, Sep 1, 2005

Research paper thumbnail of Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study

Purpose Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis an... more Purpose Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. Methods Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset[EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. Results Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of sc...

Research paper thumbnail of Content Alerts

This article cites 25 articles, 17 of which can be accessed free

Research paper thumbnail of Content Alerts

This article cites 13 articles, 5 of which can be accessed free at:

Research paper thumbnail of Molecular epidemiology of Corynebacterium diphtheriae from northwestern Russia and surrounding countries studied by using ribotyping and pulsed-field gel electrophoresis

Journal of Clinical Microbiology, 1995

A selection of 100 Corynebacterium diphtheriae isolates from asymptomatic carriers and clinical c... more A selection of 100 Corynebacterium diphtheriae isolates from asymptomatic carriers and clinical cases from five regions in northwestern Russia were examined. Six additional isolates from patients in Finland and Estonia with epidemiological links to Russia were also examined. All isolates were characterized by biotyping, toxigenicity testing, ribotyping, and pulsed-field gel electrophoresis (PFGE). Hybridization of genomic DNA digested with BstEII revealed five ribotype patterns among the biotype gravis isolates (G1 through G5) and two patterns among the biotype mitis isolates (M1 and M2). PFGE using SfiI was not able to distinguish between ribotypes G1, G2, and G4. The predominant ribotype pattern, G1, found in cases of disease in all the areas studied, appears to be disseminating, in view of the isolates received from imported cases in Finland and Estonia. Among the 106 isolates examined, 68 produced pattern G1 and 24 produced pattern M1. Most of the M1 isolates were from the Lenin...

Research paper thumbnail of Diphtheria

Nature Reviews Disease Primers, 2019

Diphtheria is an infectious disease caused by toxigenic bacteria of the Corynebacterium genus, mo... more Diphtheria is an infectious disease caused by toxigenic bacteria of the Corynebacterium genus, mostly Corynebacterium diphtheriae and rarely other closely related species, namely C. ulcerans and C. pseudo tuberculosis. The Corynebacteriaceae family comprises >100 species of aerobic, Gram-positive rods that exhibit a club-shaped morphology. Three species, C. diphtheriae, C. ulcerans and C. pseudotuberculosis, are known to produce diphtheria toxin (DT), which is encoded by a gene (tox) that is carried by a prophage and acquired by horizontal gene transfer. The tox-encoding bacteriophage integrates into specific sites of the C. diphtheriae chromosome by site-specific recombination. This bacterium was perpetuated by its eponymous name, the Klebs-Löffler bacillus, since it was first identified by Klebs in 1883 and successfully cultured by Löffler in 1884 (Fig. 1). The non-toxigenic strains of C. diphtheriae (NTCD) and Corynebacterium spp. other than C. diphtheriae are considered potential emerging pathogens as they are also capable of causing severe disease, which is not vaccine-preventable 1,2. Based on colony morpho logy and biochemical reactions, C. diphtheriae is divided into four biovars or biotypes: gravis, mitis, intermedius and belfanti. Among these, belfanti is unusually described as toxigenic 3,4 , whereas the other biotypes are named according to the disease severity they are usually associated with: serious, mild and intermediate for the gravis, mitis and intermedius biotypes, respectively. Diphtheria predominantly affects children of <15 years of age, and several investigations have shown that unimmunized and immunocompromised populations are particularly vulnerable to the disease 5. Diphtheria was a major cause of childhood morbidity and mortality during the pre-vaccine era. Resurgence of this contagious disease has occurred owing to disruptions in healthcare systems and vaccination programmes. Several major outbreaks of diphtheria have been recorded during 1921-2018, in almost all global regions including the United States, Europe, Asia, the Newly Independent States of the former Soviet Union (NIS), Haiti, Venezuela and Yemen 6-10. Depending on the anatomical site affected, diphtheria can be classified into respiratory (involving the anterior nasal, pharyngeal and laryngeal cavities and the tonsils), cutaneous (including the genital area) and ocular. The typical advanced symptoms of acute diphtheria include the presence of a thick, grey layer (called the pseudomembrane) on the throat and/or tonsils, enlarged lymph node glands in the neck (bull neck) and, in severe cases, myocarditis and inflammation of the nerves. Diphtheria has a high case-fatality rate (5-17%) among the unvaccinated population, even in individuals

Research paper thumbnail of The European Diphtheria Surveillance Network (ESDN) a strong model to combat a rare disease and use resources efficiently, share knowledge openly, and give support effectively

Research paper thumbnail of Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK

Microbial Genomics, 2016

A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isol... more A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001-2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406. Analysis of the whole genome SNP-based phylogeny showed that the majority of isolates from the 2008-2009 upsurge period belonged to a distinct lineage characterized by the presence of a prophage carrying the speC exotoxin and spd1 DNAase genes but loss of two other prophages considered typical of the emm/M3 lineage. This lineage was significantly associated with the upsurge in iGAS cases and we postulate that the upsurge could be attributed in part to expansion of this novel prophagecontaining lineage within the population. The study underlines the importance of prompt genomic analysis of changes in the GAS population, providing an advanced public health warning system for newly emergent, pathogenic strains.

Research paper thumbnail of Laboratory guidelines for the diagnosis of infections caused by Corynebacterium diphtheriae and C. ulcerans. World Health Organization

Communicable disease and public health / PHLS, 1999

These guidelines represent an application of the World Health Organization European Region's ... more These guidelines represent an application of the World Health Organization European Region's manual for the laboratory diagnosis of diphtheria for laboratories in the United Kingdom (UK), but they could be applied to laboratories overseas. The manual was rewritten in response to the re-emergence of diphtheria in eastern Europe and the emergence of other infections caused by Corynebacterium diphtheriae and C. ulcerans in the UK and overseas. The guidelines summarise our current recommendations and procedures for the microbiological diagnosis of infections caused by toxigenic and non-toxigenic isolates of corynebacteria, with particular reference to C. diphtheriae and C. ulcerans.

Research paper thumbnail of Correction: Corrigendum: Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Nature Communications, 2015

The original version of this Article contained an error in the spelling of a member of the DEVANI... more The original version of this Article contained an error in the spelling of a member of the DEVANI Consortium, Lucilla Baldassarri, which was incorrectly given as Lucilia Baldassari. This has now been corrected in both the PDF and HTML versions of the Article.

Research paper thumbnail of Emergence of an Invasive Clone of Nontoxigenic Corynebacterium diphtheriae in the Urban Poor Population of Vancouver, Canada

Journal of Clinical Microbiology, 2006

Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe th... more Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae , and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.

Research paper thumbnail of Multilocus Sequence Typing Identifies Evidence for Recombination and Two Distinct Lineages of Corynebacterium diphtheriae

Journal of Clinical Microbiology, 2010

We describe the development of a multilocus sequence typing (MLST) scheme for Corynebacterium dip... more We describe the development of a multilocus sequence typing (MLST) scheme for Corynebacterium diphtheriae , the causative agent of the potentially fatal upper respiratory disease diphtheria. Global changes in diphtheria epidemiology are highlighted by the recent epidemic in the former Soviet Union (FSU) and also by the emergence of nontoxigenic strains causing atypical disease. Although numerous techniques have been developed to characterize C. diphtheriae , their use is hindered by limited portability and, in some instances, poor reproducibility. One hundred fifty isolates from 18 countries and encompassing a period of 50 years were analyzed by multilocus sequence typing (MLST). Strain discrimination was in accordance with previous ribotyping data, and clonal complexes associated with disease outbreaks were clearly identified by MLST. The data produced are portable, reproducible, and unambiguous. The MLST scheme described provides a valuable tool for monitoring and characterizing e...

Research paper thumbnail of International External Quality Assurance for Laboratory Diagnosis of Diphtheria

Journal of Clinical Microbiology, 2009

The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers f... more The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Ma...

Research paper thumbnail of Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae , Streptococcus oralis , and Streptococcus mitis : Characterization of “Atypical” Pneumococci and Organisms Allied to S. mitis Harboring S. pneumoniae Virulence Factor-Encoding Genes

Infection and Immunity, 2000

The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized spe... more The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus ( Streptococcus pneumoniae ), an important human pathogen, is traditionally distinguished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three differentiating characteristics: optochin susceptibility, bile solubility, and agglutination with antipneumococcal polysaccharide capsule antibodies. However, there are many reports in the literature of pneumococci lacking one or more of these defining characteristics. Sometimes called “atypical” pneumococci, these isolates can be the source of considerable confusion in the clinical laboratory. Little is known to date about the genetic relationships of such organisms with classical S. pneumoniae isolates. Here we describe these relationsh...

Research paper thumbnail of Diphtheria in the 1990s: Return of an old adversary

Clinical Microbiology and Infection, 1995

Kingdom; and 21ntensive Care Unit for Patients with Infectious Diseases, B o t l n Hospital, Mosc... more Kingdom; and 21ntensive Care Unit for Patients with Infectious Diseases, B o t l n Hospital, Moscow, Federation of Russia Readers are invited to use this article as a selfassessment exercise and to update their knowledge.

Research paper thumbnail of External Quality Assessment for the Determination of Diphtheria Antitoxin in Human Serum

Clinical and Vaccine Immunology, 2010

ABSTRACTAccurate determination of diphtheria toxin antibodies is of value in determining the rate... more ABSTRACTAccurate determination of diphtheria toxin antibodies is of value in determining the rates of immunity within broad populations or the immune status of individuals who may be at risk of infection, by assessing responses to vaccination and immunization schedule efficacy. Here we report the results of an external quality assessment (EQA) study for diphtheria serology, performed within the dedicated surveillance network DIPNET. Twelve national laboratories from 11 European countries participated by testing a standard panel of 150 sera using their current routine method: Vero cell neutralization test (NT), double-antigen enzyme-linked immunosorbent assay (ELISA; DAE), dual double-antigen time-resolved fluorescence immunoassay (dDA-DELFIA), passive hemagglutination assay (PHA), toxin binding inhibition assay (ToBI), and in-house or commercial ELISAs. The objective of the study was not to identify the best assay, as the advantages and drawbacks of methods used were known, but to v...

Research paper thumbnail of Current Approaches to the Laboratory Diagnosis of Diphtheria

The Journal of Infectious Diseases, 2000

Despite the success of mass immunization in many countries, diphtheria continues to play a major ... more Despite the success of mass immunization in many countries, diphtheria continues to play a major role as a potentially lethal resurgent infectious disease. Early, accurate diagnosis is imperative since delay in specific therapy may result in death. The microbiologic diagnosis of the disease, the identification of contacts and carriers, and the appropriate clinical management of these patients are therefore crucial. The epidemiology of diseases caused by Corynebacterium diphtheriae has changed dramatically over the decades, a situation that is highlighted by the resurgence of infections in the European region. These factors have strengthened the need for laboratories to screen for C. diphtheriae. Many modified and new methodologies are now used widely within laboratories for diphtheria diagnosis. Recent developments have focused upon methods for detection of the lethal and potent exotoxin produced by the causative organism, C. diphtheriae; this detection is the definitive test for the microbiologic diagnosis of diphtheria.

Research paper thumbnail of Copyright © 1997, American Society for Microbiology Corynebacterium imitans sp. nov. Isolated from Patients with Suspected Diphtheria

A 5-month-old boy of a Romanian family traveling via Ukraine to Poland developed a respiratory di... more A 5-month-old boy of a Romanian family traveling via Ukraine to Poland developed a respiratory disease that resembled and that was initially diagnosed as pharyngeal diphtheria. The child recovered after treatment with antidiphtheria antitoxin. A coryneform bacterium had been isolated from a nasopharyngeal specimen from the child and was initially identified as an atypical Corynebacterium diphtheriae strain. Seven adults who had contact with either the child or an adult contact person also developed symptoms of pharyngeal diphtheria, were also treated with antitoxin, and recovered uneventfully. Coryneform bacteria similar to that originating from the index patient were also isolated from the throat swabs of three adults. Detailed biochemical and chemotaxonomic investigations revealed that the coryneform bacteria belonged to the genus Corynebacterium and could be differentiated from all other defined species of this genus. Ribotyping and pulsed-field gel electrophoresis demonstrated t...

Research paper thumbnail of Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010

Eurosurveillance, 2010

We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterina... more We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified.

Research paper thumbnail of Invasive Group A<i>Streptococcus</i>Infection among Children, Rural Kenya

Emerging Infectious Diseases, Feb 1, 2016

To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the s... more To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998-2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person-years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type-specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence.

Research paper thumbnail of Characterization of Toxigenic <i>Corynebacterium ulcerans</i> Strains Isolated from Humans and Domestic Cats in the United Kingdom

Journal of Clinical Microbiology, Sep 1, 2005

Research paper thumbnail of Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study

Purpose Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis an... more Purpose Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. Methods Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset[EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. Results Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of sc...

Research paper thumbnail of Content Alerts

This article cites 25 articles, 17 of which can be accessed free

Research paper thumbnail of Content Alerts

This article cites 13 articles, 5 of which can be accessed free at:

Research paper thumbnail of Molecular epidemiology of Corynebacterium diphtheriae from northwestern Russia and surrounding countries studied by using ribotyping and pulsed-field gel electrophoresis

Journal of Clinical Microbiology, 1995

A selection of 100 Corynebacterium diphtheriae isolates from asymptomatic carriers and clinical c... more A selection of 100 Corynebacterium diphtheriae isolates from asymptomatic carriers and clinical cases from five regions in northwestern Russia were examined. Six additional isolates from patients in Finland and Estonia with epidemiological links to Russia were also examined. All isolates were characterized by biotyping, toxigenicity testing, ribotyping, and pulsed-field gel electrophoresis (PFGE). Hybridization of genomic DNA digested with BstEII revealed five ribotype patterns among the biotype gravis isolates (G1 through G5) and two patterns among the biotype mitis isolates (M1 and M2). PFGE using SfiI was not able to distinguish between ribotypes G1, G2, and G4. The predominant ribotype pattern, G1, found in cases of disease in all the areas studied, appears to be disseminating, in view of the isolates received from imported cases in Finland and Estonia. Among the 106 isolates examined, 68 produced pattern G1 and 24 produced pattern M1. Most of the M1 isolates were from the Lenin...

Research paper thumbnail of Diphtheria

Nature Reviews Disease Primers, 2019

Diphtheria is an infectious disease caused by toxigenic bacteria of the Corynebacterium genus, mo... more Diphtheria is an infectious disease caused by toxigenic bacteria of the Corynebacterium genus, mostly Corynebacterium diphtheriae and rarely other closely related species, namely C. ulcerans and C. pseudo tuberculosis. The Corynebacteriaceae family comprises >100 species of aerobic, Gram-positive rods that exhibit a club-shaped morphology. Three species, C. diphtheriae, C. ulcerans and C. pseudotuberculosis, are known to produce diphtheria toxin (DT), which is encoded by a gene (tox) that is carried by a prophage and acquired by horizontal gene transfer. The tox-encoding bacteriophage integrates into specific sites of the C. diphtheriae chromosome by site-specific recombination. This bacterium was perpetuated by its eponymous name, the Klebs-Löffler bacillus, since it was first identified by Klebs in 1883 and successfully cultured by Löffler in 1884 (Fig. 1). The non-toxigenic strains of C. diphtheriae (NTCD) and Corynebacterium spp. other than C. diphtheriae are considered potential emerging pathogens as they are also capable of causing severe disease, which is not vaccine-preventable 1,2. Based on colony morpho logy and biochemical reactions, C. diphtheriae is divided into four biovars or biotypes: gravis, mitis, intermedius and belfanti. Among these, belfanti is unusually described as toxigenic 3,4 , whereas the other biotypes are named according to the disease severity they are usually associated with: serious, mild and intermediate for the gravis, mitis and intermedius biotypes, respectively. Diphtheria predominantly affects children of <15 years of age, and several investigations have shown that unimmunized and immunocompromised populations are particularly vulnerable to the disease 5. Diphtheria was a major cause of childhood morbidity and mortality during the pre-vaccine era. Resurgence of this contagious disease has occurred owing to disruptions in healthcare systems and vaccination programmes. Several major outbreaks of diphtheria have been recorded during 1921-2018, in almost all global regions including the United States, Europe, Asia, the Newly Independent States of the former Soviet Union (NIS), Haiti, Venezuela and Yemen 6-10. Depending on the anatomical site affected, diphtheria can be classified into respiratory (involving the anterior nasal, pharyngeal and laryngeal cavities and the tonsils), cutaneous (including the genital area) and ocular. The typical advanced symptoms of acute diphtheria include the presence of a thick, grey layer (called the pseudomembrane) on the throat and/or tonsils, enlarged lymph node glands in the neck (bull neck) and, in severe cases, myocarditis and inflammation of the nerves. Diphtheria has a high case-fatality rate (5-17%) among the unvaccinated population, even in individuals

Research paper thumbnail of The European Diphtheria Surveillance Network (ESDN) a strong model to combat a rare disease and use resources efficiently, share knowledge openly, and give support effectively

Research paper thumbnail of Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK

Microbial Genomics, 2016

A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isol... more A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001-2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406. Analysis of the whole genome SNP-based phylogeny showed that the majority of isolates from the 2008-2009 upsurge period belonged to a distinct lineage characterized by the presence of a prophage carrying the speC exotoxin and spd1 DNAase genes but loss of two other prophages considered typical of the emm/M3 lineage. This lineage was significantly associated with the upsurge in iGAS cases and we postulate that the upsurge could be attributed in part to expansion of this novel prophagecontaining lineage within the population. The study underlines the importance of prompt genomic analysis of changes in the GAS population, providing an advanced public health warning system for newly emergent, pathogenic strains.

Research paper thumbnail of Laboratory guidelines for the diagnosis of infections caused by Corynebacterium diphtheriae and C. ulcerans. World Health Organization

Communicable disease and public health / PHLS, 1999

These guidelines represent an application of the World Health Organization European Region's ... more These guidelines represent an application of the World Health Organization European Region's manual for the laboratory diagnosis of diphtheria for laboratories in the United Kingdom (UK), but they could be applied to laboratories overseas. The manual was rewritten in response to the re-emergence of diphtheria in eastern Europe and the emergence of other infections caused by Corynebacterium diphtheriae and C. ulcerans in the UK and overseas. The guidelines summarise our current recommendations and procedures for the microbiological diagnosis of infections caused by toxigenic and non-toxigenic isolates of corynebacteria, with particular reference to C. diphtheriae and C. ulcerans.

Research paper thumbnail of Correction: Corrigendum: Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Nature Communications, 2015

The original version of this Article contained an error in the spelling of a member of the DEVANI... more The original version of this Article contained an error in the spelling of a member of the DEVANI Consortium, Lucilla Baldassarri, which was incorrectly given as Lucilia Baldassari. This has now been corrected in both the PDF and HTML versions of the Article.

Research paper thumbnail of Emergence of an Invasive Clone of Nontoxigenic Corynebacterium diphtheriae in the Urban Poor Population of Vancouver, Canada

Journal of Clinical Microbiology, 2006

Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe th... more Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae , and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.

Research paper thumbnail of Multilocus Sequence Typing Identifies Evidence for Recombination and Two Distinct Lineages of Corynebacterium diphtheriae

Journal of Clinical Microbiology, 2010

We describe the development of a multilocus sequence typing (MLST) scheme for Corynebacterium dip... more We describe the development of a multilocus sequence typing (MLST) scheme for Corynebacterium diphtheriae , the causative agent of the potentially fatal upper respiratory disease diphtheria. Global changes in diphtheria epidemiology are highlighted by the recent epidemic in the former Soviet Union (FSU) and also by the emergence of nontoxigenic strains causing atypical disease. Although numerous techniques have been developed to characterize C. diphtheriae , their use is hindered by limited portability and, in some instances, poor reproducibility. One hundred fifty isolates from 18 countries and encompassing a period of 50 years were analyzed by multilocus sequence typing (MLST). Strain discrimination was in accordance with previous ribotyping data, and clonal complexes associated with disease outbreaks were clearly identified by MLST. The data produced are portable, reproducible, and unambiguous. The MLST scheme described provides a valuable tool for monitoring and characterizing e...

Research paper thumbnail of International External Quality Assurance for Laboratory Diagnosis of Diphtheria

Journal of Clinical Microbiology, 2009

The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers f... more The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Ma...

Research paper thumbnail of Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae , Streptococcus oralis , and Streptococcus mitis : Characterization of “Atypical” Pneumococci and Organisms Allied to S. mitis Harboring S. pneumoniae Virulence Factor-Encoding Genes

Infection and Immunity, 2000

The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized spe... more The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus ( Streptococcus pneumoniae ), an important human pathogen, is traditionally distinguished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three differentiating characteristics: optochin susceptibility, bile solubility, and agglutination with antipneumococcal polysaccharide capsule antibodies. However, there are many reports in the literature of pneumococci lacking one or more of these defining characteristics. Sometimes called “atypical” pneumococci, these isolates can be the source of considerable confusion in the clinical laboratory. Little is known to date about the genetic relationships of such organisms with classical S. pneumoniae isolates. Here we describe these relationsh...

Research paper thumbnail of Diphtheria in the 1990s: Return of an old adversary

Clinical Microbiology and Infection, 1995

Kingdom; and 21ntensive Care Unit for Patients with Infectious Diseases, B o t l n Hospital, Mosc... more Kingdom; and 21ntensive Care Unit for Patients with Infectious Diseases, B o t l n Hospital, Moscow, Federation of Russia Readers are invited to use this article as a selfassessment exercise and to update their knowledge.

Research paper thumbnail of External Quality Assessment for the Determination of Diphtheria Antitoxin in Human Serum

Clinical and Vaccine Immunology, 2010

ABSTRACTAccurate determination of diphtheria toxin antibodies is of value in determining the rate... more ABSTRACTAccurate determination of diphtheria toxin antibodies is of value in determining the rates of immunity within broad populations or the immune status of individuals who may be at risk of infection, by assessing responses to vaccination and immunization schedule efficacy. Here we report the results of an external quality assessment (EQA) study for diphtheria serology, performed within the dedicated surveillance network DIPNET. Twelve national laboratories from 11 European countries participated by testing a standard panel of 150 sera using their current routine method: Vero cell neutralization test (NT), double-antigen enzyme-linked immunosorbent assay (ELISA; DAE), dual double-antigen time-resolved fluorescence immunoassay (dDA-DELFIA), passive hemagglutination assay (PHA), toxin binding inhibition assay (ToBI), and in-house or commercial ELISAs. The objective of the study was not to identify the best assay, as the advantages and drawbacks of methods used were known, but to v...

Research paper thumbnail of Current Approaches to the Laboratory Diagnosis of Diphtheria

The Journal of Infectious Diseases, 2000

Despite the success of mass immunization in many countries, diphtheria continues to play a major ... more Despite the success of mass immunization in many countries, diphtheria continues to play a major role as a potentially lethal resurgent infectious disease. Early, accurate diagnosis is imperative since delay in specific therapy may result in death. The microbiologic diagnosis of the disease, the identification of contacts and carriers, and the appropriate clinical management of these patients are therefore crucial. The epidemiology of diseases caused by Corynebacterium diphtheriae has changed dramatically over the decades, a situation that is highlighted by the resurgence of infections in the European region. These factors have strengthened the need for laboratories to screen for C. diphtheriae. Many modified and new methodologies are now used widely within laboratories for diphtheria diagnosis. Recent developments have focused upon methods for detection of the lethal and potent exotoxin produced by the causative organism, C. diphtheriae; this detection is the definitive test for the microbiologic diagnosis of diphtheria.

Research paper thumbnail of Copyright © 1997, American Society for Microbiology Corynebacterium imitans sp. nov. Isolated from Patients with Suspected Diphtheria

A 5-month-old boy of a Romanian family traveling via Ukraine to Poland developed a respiratory di... more A 5-month-old boy of a Romanian family traveling via Ukraine to Poland developed a respiratory disease that resembled and that was initially diagnosed as pharyngeal diphtheria. The child recovered after treatment with antidiphtheria antitoxin. A coryneform bacterium had been isolated from a nasopharyngeal specimen from the child and was initially identified as an atypical Corynebacterium diphtheriae strain. Seven adults who had contact with either the child or an adult contact person also developed symptoms of pharyngeal diphtheria, were also treated with antitoxin, and recovered uneventfully. Coryneform bacteria similar to that originating from the index patient were also isolated from the throat swabs of three adults. Detailed biochemical and chemotaxonomic investigations revealed that the coryneform bacteria belonged to the genus Corynebacterium and could be differentiated from all other defined species of this genus. Ribotyping and pulsed-field gel electrophoresis demonstrated t...