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Background: The burden of Aedes aegypti-transmitted viruses such as dengue, chikungunya, and Zika are increasing globally, fueled by urbanization and climate change, with some of the highest current rates of transmission in Asia. Local factors in the built environment have the potential to exacerbate or mitigate transmission., Methods: In 24 informal urban settlements in Makassar, Indonesia and Suva, Fiji, we tested children under 5 years old for evidence of prior infection with dengue, chikungunya, and Zika viruses by IgG serology. We used a catalytic model using seroprevalence and mean age to estimate annual incidence of dengue in each country. We also conducted detailed questionnaires to evaluate environmental risk factors for a positive serology result. Dengue risk factors were evaluated for children by univariate and multivariable logistic regression accounting for settlement as a fixed effect. Trash and flooding were additionally evaluated as dengue risk factors at the settlement level by univariate linear regression., Results: In Fiji and Indonesia respectively, 46% and 33% of children under 5 years old were seropositive for dengue, 3% and 3% for chikungunya, and 9% and 2% for Zika. In Indonesia, children living in a household where trash is routinely collected and removed were significantly less likely to be dengue seropositive in both unadjusted and adjusted models [adjusted model: OR 0.3 (95% CI: 0.1-0.8)]. In Indonesia, settlements with a higher proportion of households reporting flooding also had lower dengue rates (slope = 0.44; p-value: <0.05)., Conclusions: Household trash collection and community flood management are important targets for interventions to mitigate the increasing risk of Aedes aegypti-transmitted viruses., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics review and approval was provided by participating universities and local IRBs, including: Monash University Human Research Ethics Committee (Melbourne, Australia; project ID 35903), Ministry of Research, Technology and Higher Education Ethics Committee of Medical Research at the Faculty of Medicine, Universitas Hasanuddin (Makassar, Indonesia; protocol UH18020110), and Fiji National University College Human Health Research Ethics Committee (CHREC ID 137.19). Written informed consent was obtained from the parents/guardians of all child participants. Consent for publication: Not applicable. Competing interests: None of the authors have any relevant conflict of interest or other financial disclosures relevant to the subject matter., (© 2024. The Author(s).)

There is a significant challenge in global health and development research that pivots on the difficulties of delivering (cost-)effective treatments or interventions that are scalable andtransferable across settings. That is, how does one deliver "true effects", proven treatments, into new settings? This is often addressed in pragmatic trials or implementation research in which one makes adjustments to the delivery of the treatment to ensure that it works here and there. In this critical analytical review, we argue that the approach mis-characterises the cause-effect relationship and fails to recognise the local, highly contextual nature of what it means to say an intervention "works". We use an ongoing randomised controlled trial (RCT)-an informal settlement redevelopment intervention in Indonesia and Fiji to reduce human exposure to pathogenic faecal contamination-as a vehicle for exploring the ideas and implications of identifying interventions that work in global health and development. We describe the highly contextualised features of the research and the challenges these would pose in attempts to generalise the results. In other words, we detail that which is frequently elided from most RCTs. As our critical lens, we us the work of American philosopher, Nancy Cartwright, who argued that research produces dappled regions of causal insights-lacunae against a backdrop of causal ignorance. Rather than learn about a relationship between a treatment and an outcome, we learn that in the right sort of context, a treatment reliably produces a particular outcome. Moving a treatment from here to there becomes, therefore, something of an engineering exercise to ensure the right factors (or "shields") are in place so the cause-effect is manifest. As a consequence, one cannot assume that comparative effectiveness or cost-effectiveness would be maintained., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Multiple bacteria, viruses, protists, and helminths cause enteric infections that greatly impact human health and wellbeing. These enteropathogens are transmited via several pathways through human, animal, and environmental reservoirs. Individual qPCR assays have been extensively used to detect enteropathogens within these types of samples, whereas the TaqMan array card (TAC), which allows simultaneous detection of multiple enteropathogens, has only previously been validated in human clinical samples., Methods: In this methodological comparison study, we compared the performance of a custom 48-singleplex TAC relative to standard qPCR. We established the sensitivity and specificity of each method for the detection of eight enteric targets, by using spiked samples with varying levels of PCR inhibition. We then tested the prevalence and abundance of pathogens in wastewater from Melbourne (Australia), and human, animal, and environmental samples from informal settlements in Suva, Fiji using both TAC and qPCR., Findings: Both methods exhibited similarly h specificity (TAC 100%, qPCR 94%), sensitivity (TAC 92%, qPCR 100%), and quantitation accuracy (TAC 91%, qPCR 99%) in non-inhibited sample matrices with spiked gene fragments. PCR inhibitors substantially affected detection via TAC, though this issue was alleviated by ten-fold sample dilution. Among samples from informal settlements, the two techniques performed similarly for detection (89% agreement) and quantitation (R 2 0·82) for the eight enteropathogen targets. The TAC additionally included 38 other enteric targets, enabling detection of diverse faecal pathogens and extensive environmental contamination that would be prohibitively labour intensive to assay by standard qPCR., Interpretation: The two techniques produced similar results across diverse sample types, with qPCR prioritising greater sensitivity and quantitation accuracy, and TAC trading small reductions in these for a cost-effective larger enteropathogen panel enabling a greater number of enteric pathogens to be analysed concurrently, which is beneficial given the abundance and variety of enteric pathogens in environments such as urban informal settlements. The ability to monitor multiple enteric pathogens across diverse reservoirs could allow better resolution of pathogen exposure pathways, and the design and monitoring of interventions to reduce pathogen load., Funding: Wellcome Trust Our Planet, Our Health programme., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries., Methods and Analysis: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being., Ethics: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University., Trial Registration Number: ACTRN12618000633280; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)