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Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles.

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INTRODUCTION: Complex trauma can have serious impacts on the health and well-being of Aboriginal and Torres Strait Islander families. The perinatal period represents a 'critical window' for recovery and transforming cycles of trauma into cycles of healing. The Healing the Past by Nurturing the Future (HPNF) project aims to implement and evaluate a programme of strategies to improve support for Aboriginal and Torres Strait islander families experiencing complex trauma. METHOD: The HPNF programme was codesigned over 4 years to improve awareness, support, recognition and assessment of trauma. Components include (1) a trauma-aware, healing-informed training and resource package for service providers; (2) trauma-awareness resources for parents; (3) organisational readiness assessment; (4) a database for parents and service providers to identify accessible and appropriate additional support and (5) piloting safe recognition and assessment processes. The programme will be implemented in a large rural health service in Victoria, Australia, over 12 months. Evaluation using a mixed-methods approach will assess feasibility, acceptability, cost, effectiveness and sustainability. This will include service user and provider interviews; service usage and cost auditing; and an administrative linked data study of parent and infant outcomes. ANALYSIS: Qualitative data will be analysed using reflexive thematic analysis. Quantitative and service usage outcomes will be described as counts and proportions. Evaluation of health outcomes will use interrupted time series analyses. Triangulation of data will be conducted and mapped to the Consolidated Framework for Implementation Research and Reach, Effectiveness, Adoption, Implementation and Maintenance frameworks to understand factors influencing feasibility, acceptability, effectiveness, cost and sustainability. ETHICS AND DISSEMINATION: Approval granted from St Vincent's Melbourne Ethics Committee (approval no. 239/22). Data will be disseminated according to the strategy outlined in the codesign study protocol, in-line with the National Health and Medical Research Council Aboriginal and Torres Strait Islander Research Excellence criteria.

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Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.

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