Streptococcus pyogenes
or group A streptococcus (GAS) causes mild to severe infections in humans. GAS genotype
emm1
is the leading cause of invasive disease worldwide. In the Nordic countries
emm28
...has been the dominant type since the 1980s. Recently, a resurgence of genotype
emm1
was reported from Sweden. Here we present the epidemiology of invasive GAS (iGAS) infections and their association with emm-types in Norway from 2010–2014. We retrospectively collected surveillance data on antimicrobial susceptibility, multilocus sequence type and emm-type, and linked them with demographic and clinical manifestation data to calculate age and sex distributions, major emm- and sequence types and prevalence ratios (PR) on associations between emm-types and clinical manifestations. We analysed 756 iGAS cases and corresponding isolates, with overall incidence of 3.0 per 100000, median age of 59 years (range, 0–102), and male 56 %. Most frequent clinical manifestation was sepsis (49 %) followed by necrotizing fasciitis (9 %). Fifty-two different emm-types and 67 sequence types were identified, distributed into five evolutionary clusters. The most prevalent genotype was
emm1
(ST28) in all years (range, 20–33 %) followed by 15 %
emm28
in 2014. All isolates were susceptible to penicillin, 15 % resistant to tetracycline and <4 % resistant to erythromycin. A PR of 4.5 (95 % CI, 2.3–8.9) was calculated for
emm2
and necrotizing fasciitis. All
emm22
isolates were resistant to tetracycline PR 7.5 (95 % CI, 5.8–9.9). This study documented the dominance of
emm1
, emergence of
emm89
and probable import of tetracycline resistant
emm112.2
into Norway (2010–2014). Genotype fluctuations between years suggested a mutual exclusive dominance of evolutionary clades.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background A serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of ...its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. Methods We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA–TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1–29 years of a rural area roughly 13–15 and 2–4 months before and 4–6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Findings Roughly 1·8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100 000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100 000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046–0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2–4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4–6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002–0·138; p<0·0001). Interpretation PSA–TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. Funding The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate ...Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13.
A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians. Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child's health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal isolates were examined with susceptibility testing, serotyping and multilocus sequence typing.
The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones Norway
-42 and Poland
-20, as well as penicillin- and macrolide-susceptible clone Netherlands
-31. A high level of antimicrobial consumption was noted by the study. According to the parent's reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models.
The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundMeningococcal epidemics in Africa are generally caused by capsular group A strains, but W-135 or X strains also cause epidemics in this region. Factor H–binding protein (fHbp) is a novel ...antigen being investigated for use in group B vaccines. Little is known about fHbp in strains from other capsular groups MethodsWe investigated fHbp in 35 group A, W-135, and X strains from Africa ResultsThe 22 group A isolates, which included each of the sequence types (STs) responsible for epidemics since 1963, and 4 group X and 3 group W-135 isolates from recent epidemics had genes encoding fHbp in antigenic variant group 1. The remaining 6 W-135 isolates had fHbp variant 2. Within each fHbp variant group, there was 92%–100% amino acid identity, and the proteins expressed conserved epitopes recognized by bactericidal monoclonal antibodies. Serum samples obtained from mice vaccinated with native outer membrane vesicle vaccines from mutants engineered to express fHbp variants had broad bactericidal activity against group A, W-135, or X strains ConclusionsDespite extensive natural exposure of the African population, fHbp is conserved among African strains. A native outer membrane vesicle vaccine that expresses fHbp variants can potentially elicit protective antibodies against strains from all capsular groups that cause epidemics in the region
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Strains of Staphylococcus aureus obtained from bovine (n = 117) and caprine (n = 114) bulk milk were characterized and compared with S. aureus strains from raw-milk products (n = 27), bovine mastitis ...specimens (n = 9), and human blood cultures (n = 39). All isolates were typed by pulsed-field gel electrophoresis (PFGE). In addition, subsets of isolates were characterized using multilocus sequence typing (MLST), multiplex PCR (m-PCR) for genes encoding nine of the staphylococcal enterotoxins (SE), and the cloverleaf method for penicillin resistance. A variety of genotypes were observed, and greater genetic diversity was found among bovine than caprine bulk milk isolates. Certain genotypes, with a wide geographic distribution, were common to bovine and caprine bulk milk and may represent ruminant-specialized S. aureus. Isolates with genotypes indistinguishable from those of strains from ruminant mastitis were frequently found in bulk milk, and strains with genotypes indistinguishable from those from bulk milk were observed in raw-milk products. This indicates that S. aureus from infected udders may contaminate bulk milk and, subsequently, raw-milk products. Human blood culture isolates were diverse and differed from isolates from other sources. Genotyping by PFGE, MLST, and m-PCR for SE genes largely corresponded. In general, isolates with indistinguishable PFGE banding patterns had the same SE gene profile and isolates with identical SE gene profiles were placed together in PFGE clusters. Phylogenetic analyses agreed with the division of MLST sequence types into clonal complexes, and isolates within the same clonal complex had the same SE gene profile. Furthermore, isolates within PFGE clusters generally belonged to the same clonal complex.
Teenagers have a higher risk of invasive meningococcal disease (IMD) than the general population. This cross-sectional study aimed to characterise strains of Neisseria meningitidis circulating among ...Norwegian teenagers and to assess risk factors for meningococcal carriage. Oropharyngeal swabs were collected from secondary-school students in southeastern Norway in 2018-2019. Meningococcal isolates were characterised using whole genome sequencing. Risk factors for meningococcal carriage were assessed from questionnaire data. Samples were obtained from 2296 12-24-year-olds (majority 13-19-year-olds). N. meningitidis was identified in 167 (7.3%) individuals. The highest carriage rate was found among 18-year-olds (16.4%). Most carriage isolates were capsule null (40.1%) or genogroup Y (33.5%). Clonal complexes cc23 (35.9%) and cc198 (32.3%) dominated and 38.9% of carriage strains were similar to invasive strains currently causing IMD in Norway. Use of Swedish snus (smokeless tobacco) (OR 1.56, 95% CI 1.07-2.27), kissing >two persons/month (OR 2.76, 95% CI 1.49-5.10) and partying >10 times/3months (OR 3.50, 95% CI 1.45-8.48) were associated with carriage, while age, cigarette smoking, sharing of drinking bottles and meningococcal vaccination were not. The high meningococcal carriage rate among 18-year-olds is probably due to risk-related behaviour. Use of Swedish snus is possibly a new risk factor for meningococcal carriage. Almost 40% of circulating carriage strains have invasive potential.
Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To ...overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of ≈ 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Meningococcal conjugate vaccines induce serum antibodies crucial for protection against invasive disease. Salivary antibodies are believed to be important for hindering meningococcal acquisition ...and/or clearance of established carriage. In this study, we measured salivary IgA and IgG antibodies induced by vaccination with a monovalent serogroup A conjugate vaccine or a tetravalent A, C, W and Y conjugate vaccine, in comparison with antibody levels in serum. Saliva and serum samples from Ethiopian volunteers (1–29 years) collected before and eight times on a weekly basis after receiving the serogroup A conjugate vaccine, the tetravalent serogroup A, C, W and Y conjugate vaccine, or no vaccine (control group), were analysed using a multiplex microsphere immunoassay for antibody detection. Serogroup‐specific IgG antibody levels in saliva increased significantly after vaccination with both vaccines. The monovalent serogroup A vaccine also induced an increase in salivary IgA antibodies. A strong correlation between serogroup‐specific IgG antibodies in saliva and serum, and a somewhat lower correlation for IgA, was observed for all serogroups. There was also a strong correlation between specific secretory IgA and IgA antibodies in saliva for all serogroups. Meningococcal conjugate vaccines are able to elicit salivary antibodies against serogroup A, C, W and Y correlating with antibody levels in serum. The strong correlation between saliva and serum antibody levels indicates that saliva may be used as a surrogate of systemic antibody responses.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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