Mevalonate Biosynthesis Intermediates Are Key Regulators of Innate Immunity in Bovine Endometritis

Metabolic changes can influence inflammatory responses to bacteria. To examine whether localized manipulation of the mevalonate pathway impacts innate immunity, we exploited a unique mucosal disease model, endometritis, where inflammation is a consequence of innate immunity. IL responses to pathogenic bacteria and LPS were modulated in bovine endometrial cell and organ cultures by small molecules that target the mevalonate pathway. Treatment with multiple statins, bisphosphonates, squalene synthase inhibitors, and small interfering RNA showed that inhibition of farnesyl-diphosphate farnesyl transferase (squalene synthase), but not 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyl diphosphate synthase, reduced endometrial organ and cellular inflammatory responses to pathogenic bacteria and LPS. Although manipulation of the mevalonate pathway reduced cellular cholesterol, impacts on inflammation were independent of cholesterol concentration as cholesterol depletion using cyclodextrins did not alter inflammatory responses. Treatment with the isoprenoid mevalonate pathway-intermediates, farnesyl diphosphate and geranylgeranyl diphosphate, also reduced endometrial cellular inflammatory responses to LPS. These data imply that manipulating the mevalonate pathway regulates innate immunity within the endometrium, and that isoprenoids are regulatory molecules in this process, knowledge that could be exploited for novel therapeutic strategies

Global rabies control: the role of international organisations and the Global Strategic Plan to eliminate dog-mediated human rabies

International partners are united to reach the shared goal of zero dog-mediated human rabies deaths by 2030, worldwide. Under the Tripartite collaboration, the World Health Organization, the World Organisation for Animal Health and the Food and Agriculture Organization of the United Nations are prioritising rabies as a model for 'One Health' in action. In 2015, the Global Rabies Conference led to the development of the Global Framework for the Elimination of Dog-Mediated Human Rabies. This long-term strategy centres around five pillars of rabies elimination (STOP-R): i)Sociocultural; ii)Technical; iii) Organisational; iv)Political; and v) Resources. Together with their partners, the Tripartite are working to operationalise the Framework through: i) engaging communities to build rabies awareness; ii) strengthening human and animal health systems, surveillance, and providing proof of concept that rabies elimination is feasible; iii) promoting intersectoral and regional collaboration; iv) advocating for political engagement and support; and v) building the case for investment through public-private partnerships and a Global Strategic Plan to end human deaths from dog-mediated rabies. By creating an enabling environment for countries to prioritise rabies and implement existing tools, the Tripartite are committed to catalysing change, empowering nations and providing the necessary support to consign rabies to the history books

Evaluation of public-private partnership in the veterinary domain using impact pathway methodology: In-depth case study in the poultry sector in Ethiopia

Public–private partnerships (PPPs) in the veterinary domain are joint approaches in which public veterinary services and private actors such as private veterinarians, producers' associations, or private companies work together to address complex animal health challenges. They are implemented worldwide and can help to strengthen the capacities of veterinary services, but few have been evaluated. None of the evaluations developed in the veterinary domain explicitly addressed PPPs, their complex program design, their evolving governance, and coordination system, and their impacts. This work represents the first application of the participatory impact pathway methodology for the evaluation of a PPP in the veterinary domain. The PPP evaluated aimed at developing the poultry sector in Ethiopia and improving poultry health service coverage, particularly in remote areas. The combination of semi-structured interviews (n = 64) and collective reflection during three workshops (n participants = 26, 48, 18), captured the viewpoints of public and private partners, actors who influenced the partnership, and actors impacted by it. The context of the PPP was analyzed, and the causal relationships between the PPP and its impacts were investigated. This work showed that collaboration between the public and private sector occurred at several administrative levels. The actors considered a variety of impacts, on the economy, business, trust, and health, which were then measured through different indicators. The actors also identified the added value of the PPP to enrich those impacts. The participatory impact pathway methodology helped to strengthen the engagement of actors in the PPP and to formulate recommendations at the policy level to favor positive results. This case study represents a milestone in building a participatory evaluation framework of PPP in the veterinary domain