Since 2014, England has seen increased scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events. We analysed changes in S pyogenes emm genotypes, and notifications of scarlet fever and invasive disease in 2014-16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as scarlet fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses. Coincident with national increases in scarlet fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p<0·0001). Sequences of emm1 isolates from 2009-16 showed emergence of a new emm1 lineage (designated M1UK)-with overlap of pharyngitis, scarlet fever, and invasive M1UK strains-which could be genotypically distinguished from pandemic emm1 isolates (M1global) by 27 single-nucleotide polymorphisms. Median SpeA protein concentration in supernatant was nine-times higher among M1UK isolates (190·2 ng/mL [IQR 168·9-200·4]; n=10) than M1global isolates (20·9 ng/mL [0·0-27·3]; n=10; p<0·0001). M1UK expanded nationally to represent 252 (84%) of all 299 emm1 genomes in 2016. Phylogenetic analysis of published datasets identified single M1UK isolates in Denmark and the USA. A dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance. UK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1_UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1_global strains, invasive M1_UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1_UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1_UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1_UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1_UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (R_t^eff) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900–38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%–1.21%) to 0.79% (95%CrI: 0.63%–0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%–35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%–10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%–10.2%) and 22.3% (95%CrI: 19.4%–25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission.

21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development. We conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0–90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001–2018). For these at-risk population groups, we summarised reported MLST and surface proteins. Based on 198 studies (29247isolates), 93–99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35–47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6–13),(4%; 95%CI:0–11) infant colonisation, and adult invasive disease (4%, 95%CI:2–6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains. A hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design.

The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.