Wood degradation by Fomitiporia mediterranea M. Fischer: Physiologic, metabolomic and proteomic approaches.

Fomitiporia mediterranea (Fmed) is one of the main fungal species found in grapevine wood rot, also called "amadou," one of the most typical symptoms of grapevine trunk disease Esca. This fungus is functionally classified as a white-rot, able to degrade all wood structure polymers, i.e., hemicelluloses, cellulose, and the most recalcitrant component, lignin. Specific enzymes are secreted by the fungus to degrade those components, namely carbohydrate active enzymes for hemicelluloses and cellulose, which can be highly specific for given polysaccharide, and peroxidases, which enable white-rot to degrade lignin, with specificities relating to lignin composition as well. Furthermore, besides polymers, a highly diverse set of metabolites often associated with antifungal activities is found in wood, this set differing among the various wood species. Wood decayers possess the ability to detoxify these specific extractives and this ability could reflect the adaptation of these fungi to their specific environment. The aim of this study is to better understand the molecular mechanisms used by Fmed to degrade wood structure, and in particular its potential adaptation to grapevine wood. To do so, Fmed was cultivated on sawdust from different origins: grapevine, beech, and spruce. Carbon mineralization rate, mass loss, wood structure polymers contents, targeted metabolites (extractives) and secreted proteins were measured. We used the well-known white-rot model Trametes versicolor for comparison. Whereas no significant degradation was observed with spruce, a higher mass loss was measured on Fmed grapevine culture compared to beech culture. Moreover, on both substrates, a simultaneous degradation pattern was demonstrated, and proteomic analysis identified a relative overproduction of oxidoreductases involved in lignin and extractive degradation on grapevine cultures, and only few differences in carbohydrate active enzymes. These results could explain at least partially the adaptation of Fmed to grapevine wood structural composition compared to other wood species, and suggest that other biotic and abiotic factors should be considered to fully understand the potential adaptation of Fmed to its ecological niche. Proteomics data are available via ProteomeXchange with identifier PXD036889.

Weight of Evidence: Participatory Methods and Bayesian Updating to Contextualize Evidence Synthesis in Stakeholders' Knowledge.

Mixed methods research is well-suited to grapple with questions of what counts as valid knowledge across different contexts and perspectives. This article introduces Weight of Evidence as a transformative procedure for stakeholders to interpret, expand on and prioritize evidence from evidence syntheses, with a focus on engaging populations historically excluded from planning and decision making. This article presents the procedure's five steps using pilot data on perinatal care of immigrant women in Canada, engaging family physicians and birth companions. Fuzzy cognitive mapping offers an accessible and systematic way to generate priors to update published literature with stakeholder priorities. Weight of Evidence is a transparent procedure to broaden what counts as expertise, contributing to a more comprehensive, context-specific, and actionable understanding.

Exploration of DNA processing features unravels novel properties of ICE conjugation in Gram-positive bacteria.

Integrative and conjugative elements (ICEs) are important drivers of horizontal gene transfer in prokaryotes. They are responsible for antimicrobial resistance spread, a major current health concern. ICEs are initially processed by relaxases that recognize the binding site of oriT sequence and nick at a conserved nic site. The ICESt3/Tn916/ICEBs1 superfamily, which is widespread among Firmicutes, encodes uncanonical relaxases belonging to a recently identified family called MOBT. This family is related to the rolling circle replication initiators of the Rep_trans family. The nic site of these MOBT relaxases is conserved but their DNA binding site is still unknown. Here, we identified the bind site of RelSt3, the MOBT relaxase from ICESt3. Unexpectedly, we found this bind site distantly located from the nic site. We revealed that the binding of the RelSt3 N-terminal HTH domain is required for efficient nicking activity. We also deciphered the role of RelSt3 in the initial and final stages of DNA processing during conjugation. Especially, we demonstrated a strand transfer activity, and the formation of covalent DNA-relaxase intermediate for a MOBT relaxase.

Contributing to collaborative health governance in Africa: a realist evaluation of the Universal Health Coverage Partnership.

BACKGROUND: Policy dialogue, a collaborative governance mechanism, has raised interest among international stakeholders. They see it as a means to strengthen health systems governance and to participate in the development of health policies that support universal health coverage. In this context, WHO has set up the Universal Health Coverage Partnership. This Partnership aims to support health ministries in establishing inclusive, participatory, and evidence-informed policy dialogue. The general purpose of our study is to understand how and in what contexts the Partnership may support policy dialogue and with what outcomes. More specifically, our study aims to answer two questions: 1) How and in what contexts may the Partnership initiate and nurture policy dialogue? 2) How do collaboration dynamics unfold within policy dialogue supported by the Partnership?  METHODS: We conducted a multiple-case study realist evaluation based on Emerson's integrative framework for collaborative governance to investigate the role of the Partnership in policy dialogue on three policy issues in six sub-Saharan African countries: health financing (Burkina Faso and Democratic Republic of Congo), health planning (Cabo Verde, Niger, and Togo), and aid coordination for health (Liberia). We interviewed 121 key informants, analyzed policy documents, and observed policy dialogue events. RESULTS: The Partnership may facilitate the initiation of policy dialogue when: 1) stakeholders feel uncertain about health sector issues and acknowledge their interdependence in responding to such issues, and 2) policy dialogue coincides with their needs and interests. In this context, policy dialogue enables stakeholders to build a shared understanding of issues and of the need for action and encourages collective leadership. However, ministries' weak ownership of policy dialogue and stakeholders' lack of confidence in their capacity for joint action hinder their engagement and curb the institutionalization of policy dialogue. CONCLUSIONS: Development aid actors wishing to support policy dialogue must do so over the long term so that collaborative governance becomes routine and a culture of collaboration has time to grow. Public administrations should develop collaborative governance mechanisms that are transparent and intelligible in order to facilitate stakeholder engagement.

[Autologous hematopoietic cells for severe autoimmune diseases: Guidelines of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) for immune monitoring and biobanking]. / Suivi immunologique et collection biologique en vue de l'analyse de la réponse clinique après autogreffe de moelle pour maladies auto-immunes : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Autologous hematopoietic cell transplantation (AHCT) is a new treatment option for patients with severe autoimmune diseases (AD), based on the use of intensive or myeloablative chemotherapy to eradicate the pathogenic autoreactive immune cells and to allow the installation of a new and tolerant immune system during immune reconstitution process. Immune reconstitution analysis after AHCT is required for patients clinical follow-up and to further identify biological and immunological markers of the clinical response to develop individualized AHCT protocols. These MATHEC-SFGM-TC good clinical practice guidelines were developed by a multidisciplinary group of experts including members of the french reference center for stem Cell Therapy in Auto-immune Diseases (MATHEC), hematologists from the French speaking Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) and experts in immune monitoring and biobanking. The objectives are to provide practical recommandations for immune monitoring and biobanking of samples in patients with AD undergoing AHCT, for routine care purposes and investigational studies.

A Realist Synthesis of Community-Based Interventions in Vector-Borne Diseases.

Randomized control trials have provided evidence that some community-based interventions (CBIs) work in vector-borne diseases (VBDs). Conversely, there is limited evidence on how well those CBIs succeed in producing specific outcomes in different contexts. To conduct a realist synthesis for knowledge translation on this topic, we examined the extent to which realist concepts (context, mechanisms, and outcomes) and their relationships are present in the existing literature on CBIs for VBDs. Articles on CBIs were identified from prior scoping reviews of health interventions for VBDs. Content of the articles was extracted verbatim if it referred either to realist concepts or CBI features. The number of articles and the average number of words extracted per category per CBI were quantified. Content of the articles was scrutinized to inductively gather qualitative evidence on the interactions between realist concepts. We reviewed 41 articles on 17 CBIs from 12 countries. The average number of words used for mechanisms was much lower than those used for outcomes and context (309,474, and 836, respectively). The average number of words used for mechanisms increased when a CBI was described in three or more articles. There were more extensive accounts on CBI features than on mechanisms. It was difficult to gather evidence on the interactions among realist concepts from the content of the articles. Scarce reporting on mechanisms in published articles limits conducting a realist synthesis of CBIs in VBDs. More transdisciplinary research that goes beyond the biomedical paradigm is needed to boost the development of intervention mechanisms in this field.

Policy dialogue as a collaborative tool for multistakeholder health governance: a scoping study.

INTRODUCTION: Health system governance is the cornerstone of performant, equitable and sustainable health systems aiming towards universal health coverage. Global health actors have increasingly been using policy dialogue (PD) as a governance tool to engage with both state and non-state stakeholders. Despite attempts to frame PD practices, it remains a catch-all term for both health systems professionals and researchers. METHOD: We conducted a scoping study on PD. We identified 25 articles published in English between 1985 and 2017 and 10 grey literature publications. The analysis was guided by the following questions: (1) How do the authors define PD? (2) What do we learn about PD practices and implementation factors? (3) What are the specificities of PD in low-income and middle-income countries? RESULTS: The analysis highlighted three definitions of policy dialogue: a knowledge exchange and translation platform, a mode of governance and an instrument for negotiating international development aid. Success factors include the participants' continued and sustained engagement throughout all the relevant stages, their ability to make a constructive contribution to the discussions while being truly representative of their organisation and their high interest and stake in the subject. Prerequisites to ensuring that participants remained engaged were a clear process, a shared understanding of the goals at all levels of the PD and a PD approach consistent with the PD objective. In the context of development aid, the main challenges lie in the balance of power between stakeholders, the organisational or technical capacity of recipient country stakeholders to drive or contribute effectively to the PD processes and the increasingly technocratic nature of PD. CONCLUSION: PD requires a high level of collaborative governance expertise and needs constant, although not necessarily high, financial support. These conditions are crucial to make it a real driver of health system reform in countries' paths towards universal health coverage.

Using implementation science theories and frameworks in global health.

In global health, researchers and decision makers, many of whom have medical, epidemiology or biostatistics background, are increasingly interested in evaluating the implementation of health interventions. Implementation science, particularly for the study of public policies, has existed since at least the 1930s. This science makes compelling use of explicit theories and analytic frameworks that ensure research quality and rigour. Our objective is to inform researchers and decision makers who are not familiar with this research branch about these theories and analytic frameworks. We define four models of causation used in implementation science: intervention theory, frameworks, middle-range theory and grand theory. We then explain how scientists apply these models for three main implementation studies: fidelity assessment, process evaluation and complex evaluation. For each study, we provide concrete examples from research in Cuba and Africa to better understand the implementation of health interventions in global health context. Global health researchers and decision makers with a quantitative background will not become implementation scientists after reading this article. However, we believe they will be more aware of the need for rigorous implementation evaluations of global health interventions, alongside impact evaluations, and in collaboration with social scientists.

Sustainable, healthy cities: protocol of a mixed methods evaluation of a cluster randomized controlled trial for Aedes control in Brazil using a community mobilization approach.

BACKGROUND: Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. METHODS: The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of 3 years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, in-depth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants. DISCUSSION: The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases. TRIAL REGISTRATION: ISRCTN66131315, registration date: 1 October 2018.

Characterization of a relaxase belonging to the MOBT family, a widespread family in Firmicutes mediating the transfer of ICEs.

BACKGROUND: Conjugative spread of antibiotic resistance and virulence genes in bacteria constitutes an important threat to public health. Beyond the well-known conjugative plasmids, recent genome analyses have shown that integrative and conjugative elements (ICEs) are the most widespread conjugative elements, even if their transfer mechanism has been little studied until now. The initiator of conjugation is the relaxase, a protein catalyzing a site-specific nick on the origin of transfer (oriT) of the ICE. Besides canonical relaxases, recent studies revealed non-canonical ones, such as relaxases of the MOBT family that are related to rolling-circle replication proteins of the Rep_trans family. MOBT relaxases are encoded by ICEs of the ICESt3/ICEBs1/Tn916 superfamily, a superfamily widespread in Firmicutes, and frequently conferring antibiotic resistance. RESULTS: Here, we present the first biochemical and structural characterization of a MOBT relaxase: the RelSt3 relaxase encoded by ICESt3 from Streptococcus thermophilus. We identified the oriT region of ICESt3 and demonstrated that RelSt3 is required for its conjugative transfer. The purified RelSt3 protein is a stable dimer that provides a Mn2+-dependent single-stranded endonuclease activity. Sequence comparisons of MOBT relaxases led to the identification of MOBT conserved motifs. These motifs, together with the construction of a 3D model of the relaxase domain of RelSt3, allowed us to determine conserved residues of the RelSt3 active site. The involvement of these residues in DNA nicking activity was demonstrated by targeted mutagenesis. CONCLUSIONS: All together, this work argues in favor of MOBT being a full family of non-canonical relaxases. The biochemical and structural characterization of a MOBT member provides new insights on the molecular mechanism of conjugative transfer mediated by ICEs in Gram-positive bacteria. This could be a first step towards conceiving rational strategies to control gene transfer in these bacteria.

Realist evaluation of the role of the Universal Health Coverage Partnership in strengthening policy dialogue for health planning and financing: a protocol.

INTRODUCTION: In 2011, WHO, the European Union and Luxembourg entered into a collaborative agreement to support policy dialogue for health planning and financing; these were acknowledged as core areas in need of targeted support in countries' quest towards universal health coverage (UHC). Entitled 'Universal Health Coverage Partnership', this intervention is intended to strengthen countries' capacity to develop, negotiate, implement, monitor and evaluate robust and integrated national health policies oriented towards UHC. It is a complex intervention involving a multitude of actors working on a significant number of remarkably diverse activities in different countries. METHODS AND ANALYSIS: The researchers will conduct a realist evaluation to answer the following question: How, in what contexts, and triggering what mechanisms, does the Partnership support policy dialogue for health planning and financing towards UHC? A qualitative multiple case study will be undertaken in Togo, Liberia, Democratic Republic of Congo, Cape Verde, Burkina Faso and Niger. Three steps will be implemented: (1) formulating context-mechanism-outcome explanatory propositions to guide data collection, based on expert knowledge and theoretical literature; (2) collecting empirical data through semistructured interviews with key informants and observations of key events, and analysing data; (3) specifying the intervention theory. ETHICS AND DISSEMINATION: The primary target audiences are WHO and its partner countries; international and national stakeholders involved in or supporting policy dialogues in the health sector, especially in low-income countries; and researchers with interest in UHC, policy dialogue, evaluation research and/or realist evaluation.

Supporting Indigenous families in the Cree territory: lessons from the  Mashkûpímâtsît Awash initiative.

OBJECTIVE: We describe the adaptation of an early childcare and development program to the Indigenous context of the Cree territory in Québec. We also share lessons on the challenging implementation of home visits by Indigenous family support workers (FSWs), which is a critical component of the intervention. PARTICIPANTS: Â Mashkûpímâtsît Awash (AMA) aims to enhance the health and well-being of pregnant mothers, young children, and their families by providing intensive interdisciplinary care and follow-up. Indigenous female FSWs from the community are the key frontline workers and cornerstone of the program. SETTING: AMA is implemented as part of the multidisciplinary services provided by the Community Miyupimaatisiiun Centres (primary health care centres) in three pilot communities of Eeyou Istchee. INTERVENTION: AMA builds on family centredness and cultural safety, integration of services, and creation of family-friendly communities. It emphasizes the role of female local Indigenous FSWs in providing culturally safe outreach services in the form of home visits. OUTCOMES: The main challenge was conducting home visits. FSWs' view of the pertinence of home visits, as well as their personal stories, seemed to influence their motivation to conduct home visits. Their level of experience appeared to facilitate home visits. Encouraging creativity, fostering autonomy, ensuring a step-by-step implementation, and promoting communication were found to create a supporting environment to facilitate home visits. IMPLICATIONS: Hiring local Indigenous workers is necessary to ensure that early childhood development programs are culturally safe. Success of such programs relies on team management, provision of culturally adapted training, and quality of the ongoing emotional support provided to the FSWs.

Rien ne doit se faire pour eux sans eux : renforcer la participation des demandeurs d'asile, réfugiés et migrants sans statut et des organismes communautaires dans la recherche en santé.

The number of vulnerable migrants in Canada is on the rise. While debates on immigration policies have been at the forefront, there has been little dialogue regarding the health and well-being of refugees, asylum-seekers and non-status migrants despite the significant health inequities that these populations face. In this context, health research that aims to understand migrants' realities, develop appropriate health and social services and policies, and empower these populations, is needed more than ever. Participatory action research (PAR) is one approach for conducting relevant and empowering research with migrants, however it remains underutilized due to inadequate funding, infrastructure and support. PAR addresses real-life challenges, emphasizes collaboration with communities, and involves all stakeholders, including community-based organizations, in the co-construction and implementation of practical solutions. In this commentary, we call for more research with and for migrants, particularly in the form of PAR, as well as for more targeted funding initiatives and research conditions (University, funding agencies) that foster and support this type of research.

Impact of Cell Surface Molecules on Conjugative Transfer of the Integrative and Conjugative Element ICESt3 of Streptococcus thermophilus.

Integrative conjugative elements (ICEs) are chromosomal elements that are widely distributed in bacterial genomes, hence contributing to genome plasticity, adaptation, and evolution of bacteria. Conjugation requires a contact between both the donor and the recipient cells and thus likely depends on the composition of the cell surface envelope. In this work, we investigated the impact of different cell surface molecules, including cell surface proteins, wall teichoic acids, lipoteichoic acids, and exopolysaccharides, on the transfer and acquisition of ICESt3 from Streptococcus thermophilus The transfer of ICESt3 from wild-type (WT) donor cells to mutated recipient cells increased 5- to 400-fold when recipient cells were affected in lipoproteins, teichoic acids, or exopolysaccharides compared to when the recipient cells were WT. These mutants displayed an increased biofilm-forming ability compared to the WT, suggesting better cell interactions that could contribute to the increase of ICESt3 acquisition. Microscopic observations of S. thermophilus cell surface mutants showed different phenotypes (aggregation in particular) that can also have an impact on conjugation. In contrast, the same mutations did not have the same impact when the donor cells, instead of recipient cells, were mutated. In that case, the transfer frequency of ICESt3 decreased compared to that with the WT. The same observation was made when both donor and recipient cells were mutated. The dominant effect of mutations in donor cells suggests that modifications of the cell envelope could impair the establishment or activity of the conjugation machinery required for DNA transport.IMPORTANCE ICEs contribute to horizontal gene transfer of adaptive traits (for example, virulence, antibiotic resistance, or biofilm formation) and play a considerable role in bacterial genome evolution, thus underlining the need of a better understanding of their conjugative mechanism of transfer. While most studies focus on the different functions encoded by ICEs, little is known about the effect of host factors on their conjugative transfer. Using ICESt3 of S. thermophilus as a model, we demonstrated the impact of lipoproteins, teichoic acids, and exopolysaccharides on ICE transfer and acquisition. This opens up new avenues to control gene transfer mediated by ICEs.

Building a middle-range theory of free public healthcare seeking in sub-Saharan Africa: a realist review.

Realist reviews are a new form of knowledge synthesis aimed at providing middle-range theories (MRTs) that specify how interventions work, for which populations, and under what circumstances. This approach opens the 'black box' of an intervention by showing how it triggers mechanisms in specific contexts to produce outcomes. We conducted a realist review of health user fee exemption policies (UFEPs) in sub-Saharan Africa (SSA). This article presents how we developed both the intervention theory (IT) of UFEPs and a MRT of free public healthcare seeking in SSA, building on Sen's capability approach. Over the course of this iterative process, we explored theoretical writings on healthcare access, services use, and healthcare seeking behaviour. We also analysed empirical studies on UFEPs and healthcare access in free care contexts. According to the IT, free care at the point of delivery is a resource allowing users to make choices about their use of public healthcare services, choices previously not generally available to them. Users' ability to choose to seek free care is influenced by structural, local, and individual conversion factors. We tested this IT on 69 empirical studies selected on the basis of their scientific rigor and relevance to the theory. From that analysis, we formulated a MRT on seeking free public healthcare in SSA. It highlights three key mechanisms in users' choice to seek free public healthcare: trust, risk awareness and acceptability. Contextual elements that influence both users' ability and choice to seek free care include: availability of and control over resources at the individual level; characteristics of users' and providers' communities at the local level; and health system organization, governance and policies at the structural level.

Quatre principes de recherche pour comprendre les défis des systèmes de santé des pays à faible et moyen revenu.

In this commentary, we propose four principles for health policy and systems research in low- and middle-income countries that we think should be ingrained in research practices in this field. These principles are: complementarity of analytical perspectives; interdisciplinarity; cross-cutting knowledge; and theoretical and conceptual foundations. We illustrate each principle with the study of two reforms implemented in sub-Saharan Africa: user fee exemption policies and results-based financing. Taking these four principles into account allows a broader understanding of health systems challenges, and a nuanced approach to reflecting on each of the investigated dimensions. The examples demonstrate the interest of adopting a holistic and systemic approach to researching health systems and policies to go beyond the dominant technocratic vision, often focused on their performance and financing.

Globalization and the diffusion of ideas: why we should acknowledge the roots of mainstream ideas in global health.

Although globalization has created ample opportunities and spaces to share experiences and information, the diffusion of ideas, especially in global health, is primarily influenced by the unequal distribution of economic, political and scientific powers around the world. These ideas in global health are generally rooted in High-Income Countries (HICs), and then reach Low- and Middle-Income Countries (LMICs). We argue that acknowledging and addressing this invisible trend would contribute to a greater degree of open discussions in global health. This is expected to favor innovative, alternative, and culturally sound solutions for persistent health problems and reducing inequities.

Knowledge transfer on complex social interventions in public health: a scoping study.

OBJECTIVES: Scientific knowledge can help develop interventions that improve public health. The objectives of this review are (1) to describe the status of research on knowledge transfer strategies in the field of complex social interventions in public health and (2) to identify priorities for future research in this field. METHOD: A scoping study is an exploratory study. After searching databases of bibliographic references and specialized periodicals, we summarized the relevant studies using a predetermined assessment framework. In-depth analysis focused on the following items: types of knowledge transfer strategies, fields of public health, types of publics, types of utilization, and types of research specifications. RESULTS: From the 1,374 references identified, we selected 26 studies. The strategies targeted mostly administrators of organizations and practitioners. The articles generally dealt with instrumental utilization and most often used qualitative methods. In general, the bias risk for the studies is high. CONCLUSION: Researchers need to consider the methodological challenges in this field of research in order to improve assessment of more complex knowledge transfer strategies (when they exist), not just diffusion/dissemination strategies and conceptual and persuasive utilization.

Global health actors no longer in favor of user fees: a documentary study.

BACKGROUND: Since the advent of health user fees in low- and middle-income countries in the 1980s, the discourse of global health actors (GHAs) has changed to the disadvantage of this type of healthcare financing mechanism. The aim of the study was to identify and analyze the stance of GHAs in the debate on user fees. METHODS: We conducted documentary research using public documents published by and officially attributed to GHAs from 2005 to 2011. We categorized GHAs into four groups: intergovernmental organizations, international non-governmental organizations, government agencies, and working groups and networks. We then classified the GHAs according to their stance relative to the abolition of user fees, and conducted a thematic analysis of their discourse to understand the arguments used by each GHA to justify its stance. RESULTS: We identified 56 GHAs, for which we analyzed 140 documents. Among them, 55% were in favor of the abolition of user fees or in favor of free care at the point of delivery. None of the GHAs stated that they were in favor of user fees; however, 30% did not take a stand. Only the World Bank declares that it is both in favor of user fees and in favor of free care at point of service. GHAs generally circumscribe their stance to specific populations (pregnant women, children under 5 years, etc.) or to specific health services (primary, basic, essential). Three types of arguments are used by GHAs to justify their stance: economic, moral and ethical, and pragmatic. CONCLUSIONS: The principle of "user pays" seems to have fizzled. Production and dissemination of evidence, as well as certain advocacy networks, may have contributed to this change in discourse. However, GHAs should go a step further and translate their words into action, so that free healthcare at the point of delivery becomes a reality in low- and middle-income countries. They should provide technical and financial support to those countries that have chosen to implement user fee exemption policies, sometimes influenced by a GHA.