Parasites and childhood stunting – a mechanistic interplay with nutrition, anaemia, gut health, microbiota, and epigenetics

Funding Information: We are very grateful to the Bloomsbury Colleges grant to I.G. ( VPR.1924 ), and the Global Challenges Research Fund (A.S.R. and J.P.W.: Ref MR/S01313X/1 ) for funding. Figures created with BioRender.com .Peer reviewedPublisher PD

Guidance for evaluating integrated surveillance of antimicrobial use and resistance

Antimicrobial resistance (AMR) resulting from antimicrobial use (AMU) is an emerging threat to global health. One of the key elements for a better understanding and management of AMU and AMR is to develop effective and efficient integrated surveillance systems that consider the complex epidemiology of these issues and the impacts of resistance on humans, animals and the environment. Consequently, for this project, an international consortium of experts from multiple fields called CoEvalAMR was formed with the objectives to study user needs, characterise and compare existing tools for the evaluation of integrated AMU and AMR surveillance, apply them to case studies, and elaborate guidance on the purpose-fit selection and the use of the tools. For the comparison of evaluation tools, questions were extracted from existing tools and attributed to themes, to assess the user needs, interviews were conducted with national key stakeholders, and we applied a series of different evaluation tools to understand and document their strengths and weaknesses. The guidance was refined iteratively. From 12 evaluation tools, 1117 questions/indicators were extracted and attributed to seven emerging themes. Twenty-three experts were interviewed, who suggested to increase the ease-of-use, grant open access, provide web-based interfaces and allow results to be automatically generated. Respondents also wished for tools providing the flexibility to conduct a rapid review, or an in-depth analysis of the surveillance system, depending on the evaluation objectives. The case studies emphasised that proper evaluations require adequate resources, typically requiring the involvement of several assessors and/or stakeholders, and can take weeks or months to complete. The resulting web-based guidance comprises six main sections: 1. Introduction to surveillance evaluation, 2. Evaluation of surveillance for AMU and AMR, 3. Evaluation tools, 4. Support for selecting an evaluation tool, 5. Case studies and 6. Directory of existing tools. The audience for the guidance is personnel working in public, private, and non-governmental organisations, from public health, animal health, plant health and environmental health, at local, national and international levels. We conclude that the field is challenged by opposing user needs for reduction and simplicity versus system approaches allowing the synthesis of that knowledge to sufficiently reflect the complexity of AMU and AMR ecology for real-world decisions. The CoEvalAMR web platform allows a better understanding of the different evaluation tools and assists users in the selection of an approach that corresponds to their evaluation needs. The CoEvalAMR consortium continues to address remaining gaps and consolidate evaluation tools and approaches in the future

Sensitivity and specificity of human point-of-care circulating cathodic antigen (POC-CCA) test in African livestock for rapid diagnosis of schistosomiasis: A Bayesian latent class analysis.

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in the Afrotropical region has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. As stressed within the recent WHO NTD 2021-2030 Roadmap and Revised Guideline for schistosomiasis, inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT), Kato-Katz (KK) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity was greater in the S. curassoni-dominated Barkedji livestock, both for cattle (median 81%; 95% credible interval (CrI): 55%-98%) and small ruminants (49%; CrI: 29%-87%), than in the S. bovis-dominated Richard Toll ruminants (cattle: 62%; CrI: 41%-84%; small ruminants: 12%, CrI: 1%-37%). Overall, sensitivity was greater in cattle than in small ruminants. Small ruminants POC-CCA specificity was similar in both locations (91%; CrI: 77%-99%), whilst cattle POC-CCA specificity could not be assessed owing to the low number of uninfected cattle surveyed. Our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for cattle and possibly for predominantly S. curassoni-infected livestock, future work is needed to develop parasite- and/or livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis

Assessment of the role of gut health in childhood stunting in a multisite, longitudinal study in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol.

IntroductionChildhood stunting has a complex aetiology, with poor gut health being an important contributor. This study will assess inter-relationships between maternal and infant gut health indices and infant linear growth. Inter-relationships between gut health indices, systemic inflammation and growth hormones in early childhood will also be assessed.Methods and analysisA longitudinal observational study of cohorts of 600 newborns and their mothers in India, Indonesia and Senegal will be conducted. Women will be recruited during pregnancy and their children followed up to age 24 months. Stool, urine and blood samples will be collected from the women and children for assessments of helminthic and protozoal parasites, bacterial pathogens, faecal microbiota taxa, biomarkers of environmental enteric dysfunction, systemic inflammation and growth hormones. Child anthropometric measurements will be collected at birth and at ages 3, 6, 9, 12, 18 and 24 months. The gut health indices will be integrated with cohort data from other Action Against Stunting Hub (AASH) workstreams for interdisciplinary analyses of childhood stunting and the development of a new typology of stunting.DiscussionThis study will advance scientific understanding of the role of gut health in childhood stunting and will contribute to a broader knowledge of the complex aetiology of this condition as part of the interdisciplinary AASH research to reduce the global burden of childhood stunting.Ethics and disseminationThis study has been approved by the relevant Ethics Committees in Senegal, India, and Indonesia and LSHTM. The results will be submitted for publication in peer-reviewed journals