emm typing and validation of provisional M types for group A streptococci.

This report discusses the following issues related to typing of group A streptococci (GAS): The development and use of the 5' emm variable region sequencing (emm typing) in relation to the existing serologic typing system; the designation of emm types in relation to M types; a system for validation of new emm types; criteria for validation of provisional M types to new M-types; a list of reference type cultures for each of the M-type or emm-type strains of GAS; the results of the first culture exchange program for a quality control testing system among the national and World Health Organization collaborating centers for streptococci; and dissemination of new approaches to typing of GAS to the international streptococcal community

Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population

The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl trasferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

<p>Abstract</p> <p>Background</p> <p>The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster.</p> <p>Methods</p> <p>Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants.</p> <p>Results</p> <p>Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG.</p> <p>Conclusion</p> <p>Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood.</p

Population Genetics of Streptococcus dysgalactiae Subspecies equisimilis Reveals Widely Dispersed Clones and Extensive Recombination

Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an emerging global pathogen that can colonize and infect humans. Although most SDSE isolates possess the Lancefield group G carbohydrate, a significant minority have the group C carbohydrate. Isolates are further sub-typed on the basis of differences within the emm gene. To gain a better understanding of their molecular epidemiology and evolutionary relationships, multilocus sequence typing (MLST) analysis was performed on SDSE isolates collected from Australia, Europe and North America.The 178 SDSE isolates, representing 37 emm types, segregate into 80 distinct sequence types (STs) that form 17 clonal complexes (CCs). Eight STs recovered from all three continents account for >50% of the isolates. Thus, a small number of STs are highly prevalent and have a wide geographic distribution. Both ST and CC strongly correlate with group carbohydrate. In contrast, eleven STs were associated with >1 emm type, suggestive of recombinational replacements involving the emm gene; furthermore, 35% of the emm types are associated with genetically distant STs. Data also reveal a history of extensive inter- and intra-species recombination involving the housekeeping genes used for MLST. Sequence analysis of single locus variants identified through goeBURST indicates that genetic change mediated by recombination occurred approximately 4.4 times more frequently than by point mutation.A few genetic lineages with an intercontinental distribution dominate among SDSE causing infections in humans. The distinction between group C and G isolates reflects recent evolution, and no long-term genetic isolation between them was found. Lateral gene transfer and recombination involving housekeeping genes and the emm gene are important mechanisms driving genetic variability in the SDSE population

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders

Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health

Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis.

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders