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ABSTRACT 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.IMPORTANCEStreptococcus 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.

Introduction Secondary prophylaxis to prevent rheumatic heart disease (RHD) progression, in the form of four-weekly intramuscular benzathine benzylpenicillin G (BPG) injections, has remained unchanged since 1955. Qualitative investigations into patient preference have highlighted the need for long-acting penicillins to be delivered less frequently, ideally with reduced pain. We describe the experience of healthy volunteers participating in a phase-I safety, tolerability and pharmacokinetic trial of subcutaneous infusions of high-dose benzathine penicillin G (BPG)–the SCIP study (Australian New Zealand Clinical Trials Registry ACTRN12622000916741). Methods Participants (n = 24) received between 6.9 mL to 20.7 mL (3–9 times the standard dose) of BPG as a single infusion into the abdominal subcutaneous tissues via a spring-driven syringe pump over approximately 20 minutes. Semi-structured interviews at four time points were recorded, transcribed verbatim and thematically analysed. Tolerability and specific descriptors of the experience were explored, alongside thoughts on how the intervention could be improved for future trials in children and young adults receiving monthly BPG intramuscular injections for RHD. Results Participants tolerated the infusion well and were able describe their experiences throughout. Most reported minimal pain, substantiated via quantitative pain scores. Abdominal bruising at the infusion site did not concern participants nor impair normal activities. Insight into how SCIP could be improved for children included the use of topical analgesia, distractions via television or personal devices, a drawn-out infusion time with reduced delivery speed, and alternative infusion sites. Trust in the trial team was high. Conclusion Qualitative research is an important adjunct for early-phase clinical trials, particularly when adherence to the planned intervention is a key driver of success. These results will inform later-phase SCIP trials in people living with RHD and other indications.

Background: Little research has been published on the prevalence of rickettsial infections in Myanmar. This study determined the seroprevalence of immunoglobulin G (IgG) antibodies to rickettsial species in different regions of Myanmar. Methods: Seven hundred leftover blood samples from patients of all ages in primary care clinics and hospitals in seven regions of Myanmar were collected. Samples were screened for scrub typhus group (STG), typhus group (TG) and spotted fever group (SFG) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Immunofluorescence assays were performed for the same rickettsial groups to confirm seropositivity if ELISA optical density ≥0.5. Results: Overall IgG seroprevalence was 19% [95% confidence interval (CI) 16–22%] for STG, 5% (95% CI 3–7%) for TG and 3% (95% CI: 2–5%) for SFG. The seroprevalence of STG was particularly high in northern and central Myanmar (59% and 19–33%, respectively). Increasing age was associated with higher odds of STG and TG seropositivity [per 10-year increase, adjusted odds ratio estimate 1.68 (p < 0.01) and 1.24 (p = 0.03), respectively]. Conclusion: Rickettsial infections are widespread in Myanmar, with particularly high seroprevalence of STG IgG antibodies in central and northern regions. Healthcare workers should consider rickettsial infections as common causes of fever in Myanmar.

Abstract Background Aboriginal and Torres Strait Islander Australians are disproportionately affected by Chronic Hepatitis B (CHB) with a prevalence of 6.08% in the Northern Territory (NT) and liver cancer rates 6 times higher than non-Indigenous Australians. Without appropriate care, overall 25% of those living with CHB will die from either liver failure or liver cancer, outcomes that can be minimised with regular follow up, antiviral treatment and hepatocellular carcinoma (HCC) screening. This care including antiviral treatment is publicly funded in the Australian setting however the care cascade still shows inequities in access to treatment for Aboriginal Australians. We describe the impact of a mobile care delivery model, “One Stop Liver Shop”, on the cascade of care for people living with CHB in a remote Australian setting. Methods A retrospective analysis was performed for CHB care received between 2013 and 2018 in one very remote Northern Territory community, where the “One Stop Liver Shop” was iteratively developed with the community. Patients with positive Hepatitis B virus surface antigen (HBsAg) were identified through electronic medical records. Proportions of patients who are up-to-date with monitoring investigations and HCC screening were evaluated and compared to national guidelines and targets. Results Eighty-three HBsAg positive patients were evaluated. Eighty-eight percent were engaged in care, 16% of whom were receiving antiviral treatment. Liver function tests (LFT) were up to date in 71% of patients in 2013 and 88% in 2018. Viral load (VL) monitoring was up to date for 61 (73%) of patients. There were 44 patients in whom HCC screening was indicated. Of these, 38 (86.4%) were up to date with 6 monthly alpha-fetoprotein (AFP), 35 (79.5%) were up to date with 6 monthly liver ultrasound scan (USS), and 34 (77.3%) were up-to-date for both. Conclusions A “One Stop Liver Shop” developed with and including Aboriginal Health Practitioners bridges gaps in the availability of services to those living with CHB in a very remote community and improves the cascade of care.