Evaluating the role of surgical sterilisation in canine rabies control: A systematic review of impact and outcomes

© 2020 Collinson et al. Current recommendations for the elimination of canine-mediated human rabies focus on mass dog vaccination as the most feasible and cost-effective strategy. However, attempts to control rabies are often combined with canine surgical sterilisation programmes. The added value of sterilisation is widely debated. A systematic review was undertaken to compare the outcomes and impact of vaccination and sterilisation programmes with vaccination only programmes. A systematic search of three electronic databases (CAB Abstracts, Med-line and Global Health) and grey literature was performed. From 8696 abstracts found, 5554 unique studies were identified, and 16 studies met the inclusion criteria. Eight described vaccination only programmes and eight described vaccination and sterilisation programmes. Indicators of impact measured were dog bites and/or doses of post-exposure prophylaxis administered; numbers of dog and/or human rabies cases; dog population demographic changes; changes in health and welfare of dogs, and indicators related to human behaviour change. The studies were contextually very diverse, programmes being implemented were complex, and there was variation in measurement and reporting of key indicators. There-fore, it was difficult to compare the two types of intervention, and impossible to make an evaluation of the role of sterilisation, using this evidence. Given the large number of vaccination and sterilisation programmes conducted globally, the lack of studies available for review highlights a gap in data collection or reporting, essential for impact assessment. There are several knowledge gaps concerning the impact of the sterilisation component alone, as well as subsequent effects on rabies transmission and control. Prospective studies comparing the outcomes and impact of the two interventions would be required in order to establish any additional contribution of sterilisation, as well as the underlying mechanisms driving any changes. In the absence of such evidence, the priority for rabies control objectives should be implementation of mass vaccination, as currently recommended by the World Health Organisation

Priorities for Research into the Impact of Canine Surgical Sterilisation Programmes for Free-Roaming Dogs: An International Priority Setting Partnership

Surgical sterilisation is a core activity of free-roaming dog population management (DPM) programmes globally. However, there is limited published evidence on its impact at the population level. To support evidence-based decision making in this field, it is important that research conducted is relevant to those involved in working with free-roaming dogs and implementing such programmes. The aim of this study was to adapt the James Lind Alliance (JLA) user involvement approach to systematically identify the top 10 research priorities regarding the impact of canine sterilisation. International stakeholders with experience working in DPM were asked in an online survey what unanswered questions they had regarding the impact of sterilisation programmes. Thematic analysis of survey responses was used to develop a long list of collated indicative research questions (CIRQs). A literature review was performed to identify questions that were ‘true uncertainties’ (had not been answered by evidence review). These questions were reduced to a shortlist via an online interim prioritisation survey, and a Delphi consensus process determined the top 10 priorities. The top 10 questions related to dog population size and turnover, dog bite incidents, rabies control, implementation in the field and human behaviour change. These priorities were identified and shaped by people with direct experience of canine surgical sterilisation programmes, and as such are an essential resource for directing future funding and research. Addressing these priorities will generate evidence that is directly applicable to policy makers and practitioners who make decisions regarding the management of free-roaming dogs (FRDs) worldwide

Generation of left ventricle-like cardiomyocytes with improved structural, functional, and metabolic maturity from human pluripotent stem cells

Decreased left ventricle (LV) function caused by genetic mutations or injury often leads to debilitating and fatal cardiovascular disease. LV cardiomyocytes are, therefore, a potentially valuable therapeutical target. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are neither homogeneous nor functionally mature, which reduces their utility. Here, we exploit cardiac development knowledge to instruct differentiation of hPSCs specifically toward LV cardiomyocytes. Correct mesoderm patterning and retinoic acid pathway blocking are essential to generate near-homogenous LV-specific hPSC-CMs (hPSC-LV-CMs). These cells transit via first heart field progenitors and display typical ventricular action potentials. Importantly, hPSC-LV-CMs exhibit increased metabolism, reduced proliferation, and improved cytoarchitecture and functional maturity compared with age-matched cardiomyocytes generated using the standard WNT-ON/WNT-OFF protocol. Similarly, engineered heart tissues made from hPSC-LV-CMs are better organized, produce higher force, and beat more slowly but can be paced to physiological levels. Together, we show that functionally matured hPSC-LV-CMs can be obtained rapidly without exposure to current maturation regimes