Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK

Abstract

Background: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance.

Methods: We did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK. Schools and nurseries were eligible to participate if they had reported two cases of scarlet fever within 10 days of each other among children aged 2-8 years from the same class, with the most recent case arising in the preceding 48 h. We cultured throat swabs from children with scarlet fever, classroom contacts, and household contacts at four timepoints. We also cultured hand swabs and cough plates from all cases in years 1 and 2 of the study, and from classroom contacts in year 2. Surface swabs from toys and other fomites in classrooms were cultured in year 1, and settle plates from classrooms were collected in year 2. Any sample with S pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain.

Findings: Six classes, comprising 12 cases of scarlet fever, 17 household contacts, and 278 classroom contacts were recruited between March 1 and May 31, 2018 (year 1), and between March 1 and May 31, 2019 (year 2). Asymptomatic throat carriage of the outbreak strains increased from 11 (10%) of 115 swabbed children in week 1, to 34 (27%) of 126 in week 2, to 26 (24%) of 108 in week 3, and then five (14%) of 35 in week 4. Compared with carriage of outbreak S pyogenes strains, colonisation with non-outbreak and non-genotyped S pyogenes strains occurred in two (2%) of 115 swabbed children in week 1, five (4%) of 126 in week 2, six (6%) of 108 in week 3, and in none of the 35 children in week 4 (median carriage for entire study 2·8% [IQR 0·0-6·6]). Genome sequencing showed clonality of outbreak isolates within each of six classes, confirming that recent transmission accounted for high carriage. When transmissibility was tested, one (9%) of 11 asymptomatic carriers of emm4 and five (36%) of 14 asymptomatic carriers of emm3.93 had a positive cough plate. The outbreak strain was identified in only one (2%) of 60 surface swabs taken from three classrooms; however, in the two classrooms with settle plates placed in elevated locations, two (17%) of 12 and six (50%) of 12 settle plates yielded the outbreak strain.

Interpretation: Transmission of S pyogenes in schools is intense and might occur before or despite reported treatment of cases, underlining a need for rapid case management. Despite guideline adherence, heavy shedding of S pyogenes by few classroom contacts might perpetuate outbreaks, and airborne transmission has a plausible role in its spread. These findings highlight the need for research to improve understanding and to assess effectiveness of interventions to reduce airborne transmission of S pyogenes.

Funding: Action Medical Research, UK Research Innovation, and National Institute for Health Research.

Figure 1

Sample types sought from cases and contacts across all six settings Two cases were identified in setting 5 but were not recruited; however, classroom contacts of these cases were recruited. The samples provided, timings, and any breaks in sampling schedule are listed in the appendix (pp 4–6).

Figure 2

Phylogenetic tree of Streptococcus pyogenes isolates sequenced from cases, contacts, and the environment across all six settings Maximum likelihood phylogenetic tree constructed from 20 229 core single-nucleotide polymorphisms (without recombination regions), extracted after mapping 136 isolates of S pyogenes to the reference sequence H293 (emm89, HG316453.2). The outer rings (from outermost to innermost) represent the settings (1–6) and years of collection (2018 or 2019). The tips of the tree are coloured according to emm type. The shape of these tips indicates the source (ie, sample type) of individual isolates: case, classroom contact, household contact, and environmental samples from settle plate (air) or fomite (toy). In some cases and contacts, multiple isolates were detected per participant (appendix pp 4–6, 9–13). The scale bar indicates nucleotide substitution rate per site. *Singleton subtypes (emm3.143 and emm6.9) within an emm type. A detailed analysis of each setting can be found in the appendix (pp 15–18).

Figure 3

Acquisition of emm1 (M1_UK) and emm3.93 strains of Streptococcus pyogenes by classroom contacts in settings 2 (year 1) and 6 (year 2) Each icon represents an individual child, grouped by week of swabbing, in week 1 (A), week 2 (B), and week 3 (C) in setting 2 and in week 1 (D), week 2 (E), and week 3 (F) in setting 6. The colour of each icon indicates the throat swab result: negative (blue), outbreak S pyogenes strain (dark purple), non-outbreak strain or genotype not confirmed (pale purple), or participant not swabbed that week (light blue). A purple glow around the icon's head indicates a positive cough plate, around the icon's hands indicates positive hand swab, and around the whole icon indicates both a positive cough plate and hand swab. Classroom contacts had throat swabs taken on a weekly basis for at least 3 weeks after a case of scarlet fever was identified.