A review of challenges and prospects of 3D cell-based culture models used for studying drug induced liver injury during early phases of drug development.

Drug-induced liver injury (DILI) is the leading cause of compound attrition during drug development. Over the years, a battery of in-vitro cell culture toxicity tests is being conducted to evaluate the toxicity of compounds prior to testing in laboratory animals. Two-dimensional (2D) in-vitro cell culture models are commonly used and have provided a great deal of knowledge; however, these models often fall short in mimicking natural structures of tissues in-vivo. Testing in humans is the most logical method, but unfortunately there are ethical limitations associated with human tests. To overcome these limitations better human-relevant, predictive models are required. The past decade has witnessed significant efforts towards the development of three-dimensional (3D) in-vitro cell culture models better mimicking in-vivo physiology. 3D cell culture has advantages in being representative of the interactions of cells in-vivo and when validated can act as an interphase between 2D cell culture models and in-vivo animal models. The current review seeks to provide an overview of the challenges that make biomarkers used for detection of DILI not to be sensitive enough during drug development and explore how 3D cell culture models can be used to address the gap with the current models.

Sustainable education and training in laboratory animal science and ethics in low- and middle-income countries in Africa - challenges, successes, and the way forward.

Despite the recognised need for education and training in laboratory animal science (LAS) and ethics in Africa, access to such opportunities has historically been limited. To address this, the Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE) was established to pioneer a support network for the development of education and training in LAS and ethics across the African continent.In the 4.5 years since the establishment of PAN-LASE, 3635 individuals from 28 African countries have participated in our educational activities. Returning to their home institutions, they have both established and strengthened institutional and regional hubs of knowledge and competence across the continent. Additionally, PAN-LASE supported the development of guidelines for establishment of institutional Animal Ethics Committees, a critical step in the implementation of ethical review processes across the continent, and in enhancing animal welfare and scientific research standards.Key challenges and opportunities for PAN-LASE going forward include the formalisation of the network; the sustainability of education and training programmes; implementation of effective hub-and-spoke models of educational provision; strengthening governance frameworks at institutional, national and regional levels; and the availability of Africa-centric open access educational resources.Our activities are enhancing animal welfare and the quality of animal research undertaken across Africa, enabling African researchers to undertake world-leading research to offer solutions to the challenges facing the continent. The challenges, successes and the lessons learnt from PAN-LASE's journey are applicable to other low- and middle-income countries across the world seeking to enhance animal welfare, research ethics and ethical review in their own country or region.

COVID-19 disaster management plans for two laboratory animal facilities in South Africa.

Policies and guidelines are available for acute disasters such as earthquakes, fire and floods, however, little is available on how laboratory animal facilities should mitigate subacute disasters like the COVID-19 pandemic that imposed major restrictions on the free movement of people. As such, laboratory animal facilities had to find plausible mitigating measures to safeguard the welfare of animals in their care, to prevent animal suffering if staff could not reach the animals, albeit with limited time. The simplest approach was to stop active experiments and halt animal breeding, or to euthanize all animals. Challenges with such methods included the ethical debate regarding euthanasia of animals at the start of a pandemic and the need to perform a harm-benefit analysis while drafting the disaster plans, termination of studies at advanced stages with information loss or killing of genetically modified strains that would be difficult to replace.Two research animal facilities in South Africa addressed these challenges by implementing several changes such as allowing only essential studies to continue, maintaining small breeding colonies for essential strains, and providing staff with private transport for travelling to and from work to avoid public transport and risk of exposure to SARS-CoV-2. Engineering changes included redesigning working areas to cater for social distancing.The mitigating measures put in place by the two laboratory animal facilities were successful in ensuring the continued welfare of animals during the COVID-19 lockdown restrictions. These measures can be adopted in future pandemics that lead to restricted movement of staff.Plans de gestion en cas de catastrophes telles que le COVID-19 pour deux installations d'animaux de laboratoire en Afrique du Sud.

A report on the housing vervet monkeys adjacent to domestic cats as a means of environmental enrichment.

In current research guidelines, much focus is placed on ethical management of animals and the application of principles of reduction, refinement and replacement. Of these refinements through environmental enrichment is an important aspect when housing primate to prevent behavioural problems. In this study, we investigated the co-housing of domestic cats and vervet monkeys as a novel method of enrichment based on the cohabitation and stress alleviation effect of horses housed with goats and from seeing cats cohabitating with vervet monkeys in an animal sanctuary. The study used a habituation method whereby the cats were stepwise introduced to the monkeys by sight and smell but with physical separation. Assessment included changes in behaviour, weight and faecal glucocorticoid metabolite (fGCM) concentrations over time. On the first day of housing, the vervets whilst inquisitive kept their distance. The vervets housed in cages that were closest to the cats were the most active and during the first minute of introduction made more alarm calls, which stopped a few days later. The fGCMs were non-significantly different. The results of this study provide evidence that vervet monkeys and domestic cats could potentially be housed together without overt aggression. We thus suggest further observations to ascertain if the co-housing could have long-term benefits for vervet monkeys, from the companionship that would be offered by the cats.

Prevalence of antimicrobial resistance from bacterial culture and susceptibility records from horse samples in South Africa.

The continuous increase in prevalence of antimicrobial resistant bacteria presents a significant public health problem and is an indicator that antimicrobial prudent usage guidelines are not being followed, especially in developing countries. Despite trends being available from numerous countries, there is little published for South Africa. This study was aimed at estimating the prevalence and trends of antimicrobial resistance from bacterial isolates from equine clinical samples submitted for culture and susceptibility testing to the veterinary bacteriology laboratory of the University of Pretoria. The study covered a period of seven years from 2007. A total of 1505 bacterial isolates were included in this study comprising isolates from 2007 (n=447); 2008 (n=285); 2009 (n=258); 2010 (n=102); 2011 (n=89); 2012 (n=248) and 2013 (n=76). For this study, multiple drug resistance was above 50% for all the isolates. The Cochran-Armitage test showed evidence of a significantly increasing trend in prevalence of resistance to several antimicrobial agents, including amikacin (E. coli, Staphylococcus), AMX/AMP (Corynebacteria, Lactobacillus and Salmonella), chloramphenicol (Enterococcus, E. coli, Pseudomonas, Streptococcus, Staphylococcus and Salmonella), enrofloxacin (E. coli, Staphylococcus, Salmonella and Pseudomonas) and gentamicin (Salmonella, Staphylococcus). The data obtained from this study is relevant to equine practitioners, as it helps enhance the body of veterinary knowledge pertaining to antimicrobial resistance in common equine pathogens in South Africa.

An investigation of antimicrobial usage patterns by small animal veterinarians in South Africa.

AIM: At present very little information is available on antimicrobial use patterns in small animal veterinary practice in South Africa. The aim of this study was firstly to provide some indication of antimicrobial use patterns, and secondly to ascertain if the country's small animal veterinarians make use of prudent use guidelines to optimise their antimicrobial use in order to minimise the development of antimicrobial resistance. METHODOLOGY: In order to understand use patterns, a questionnaire was circulated to registered South African veterinarians, whose responses were evaluated by descriptive statistics. The prevalence of antimicrobial resistance was evaluated for dogs from samples submitted for culture and susceptibility testing for the period 2007-2013 from the only faculty of Veterinary Science in the country. The resistance data was organized into contingency tables and yearly trends in resistance evaluated by means of a chi-square. The use of antimicrobials from the survey were compared to the laboratory result to ascertain the degree of prudent use of the antimicrobials in small animal practice in a developing country. RESULTS: The responses from the questionnaire indicated that South African veterinarians predominantly (91.16%) used antimicrobials empirically before resorting to laboratory testing and that antimicrobial compounding and off label use (86.19%) of human registered medication was common practice. A worrying finding was that a large number of clients attempted antimicrobial treatment of their pets prior to seeking veterinary assistance. In terms of monitored resistance, annual prevalence of resistance was above 10% and multiple drug resistance was above 50% for all the isolates. CONCLUSION: It is concluded that antimicrobial resistant bacteria are present in small companion animal practice in South Africa which requires better implementation of prudent use guidelines.