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Controlled human infection (CHI) models can provide insights into transmission of pathogens such as Streptococcus pyogenes (Strep A). As part of the Controlled Human Infection with Penicillin for Streptococcus pyogenes (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain. Three approaches to understanding transmission were employed: the use of agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of distance droplets could spread during conversation; and environmental swabbing of high-touch items to detect Strep A on surfaces. Of the 60 (27%) CHIPS trial participants across five cohorts, 16 were enrolled in this sub-study; availability of study staff was the primary reason for selection. In total, 189 plates and 260 swabs were collected. Strep A was grown on one settle plate from a participant on the second day, using plates placed 30 cm away. This participant received the placebo dose of penicillin and had met the primary endpoint of pharyngitis. Whole-genome sequencing identified this to be the challenge strain. Strep A was not detected on any swabs. In this small sample of CHI participants, we did not find evidence of Strep A transmission by the airborne route or fomites, and just one instance of droplet spread while acutely symptomatic with streptococcal pharyngitis. Although these experiments provide evidence of minimal transmission within controlled clinical settings, greater efforts are required to explore Strep A transmission in naturalistic settings.IMPORTANCE Streptococcus pyogenes remains a significant driver of morbidity and mortality, particularly in under-resourced settings. Understanding the transmission modalities of this pathogen is essential to ensuring the success of prevention methods. This proposed paper presents a nascent attempt to determine the transmission potential of Streptococcus pyogenes nested within a larger controlled human infection model., Competing Interests: The authors declare no conflict of interest.

Background: Although Streptococcus pyogenes (Strep A) is the sixth-most common infectious disease globally, its transmission within the household remains an understudied driver of infection. We undertook a systematic review to better understand the transmission of Strep A among people within the home, while highlighting opportunities for prevention., Methods: A search strategy was applied to 5 databases between September 2022 and March 2023. Results were limited to articles published between January 2000 and March 2023. Texts were reviewed by 2 authors and the following data extracted: article details (title, author, year), study type, transmission year, country, participant age, infection status, molecular testing, and transmission mode. Funding was provided by the Australian National Health and Medical Research Council (GNT2010716)., Results: The final analysis comprised 28 texts. Only 7 studies (25.0%) provided sufficient detail to identify the Strep A transmission mode: contact (n = 4), vehicle (bedding, clothing, other fabric, and medical equipment; n = 2), and contact with animals (n = 1). All others were classified as household (specific mode unascertainable). Most articles reported outbreaks involving invasive Strep A infections., Conclusions: There is limited literature regarding household transmission of Strep A. Understanding transmission in this setting remains imperative to guide control methods., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)