Transmission and Control of African Horse Sickness in The Netherlands: A Model Analysis

African horse sickness (AHS) is an equine viral disease that is spread by Culicoides spp. Since the closely related disease bluetongue established itself in The Netherlands in 2006, AHS is considered a potential threat for the Dutch horse population. A vector-host model that incorporates the current knowledge of the infection biology is used to explore the effect of different parameters on whether and how the disease will spread, and to assess the effect of control measures. The time of introduction is an important determinant whether and how the disease will spread, depending on temperature and vector season. Given an introduction in the most favourable and constant circumstances, our results identify the vector-to-host ratio as the most important factor, because of its high variability over the country. Furthermore, a higher temperature accelerates the epidemic, while a higher horse density increases the extent of the epidemic. Due to the short infectious period in horses, the obvious clinical signs and the presence of non-susceptible hosts, AHS is expected to invade and spread less easily than bluetongue. Moreover, detection is presumed to be earlier, which allows control measures to be targeted towards elimination of infection sources. We argue that recommended control measures are euthanasia of infected horses with severe clinical signs and vector control in infected herds, protecting horses from midge bites in neighbouring herds, and (prioritized) vaccination of herds farther away, provided that transport regulations are strictly applied. The largest lack of knowledge is the competence and host preference of the different Culicoides species present in temperate regions

Assessing the potential for Bluetongue virus 8 to spread and vaccination strategies in Scotland

Europe has seen frequent outbreaks of Bluetongue (BT) disease since 2006, including an outbreak of BT virus serotype 8 in central France during 2015 that has continued to spread in Europe during 2016. Thus, assessing the potential for BTv-8 spread and determining the optimal deployment of vaccination is critical for contingency planning. We developed a spatially explicit mathematical model of BTv-8 spread in Scotland and explored the sensitivity of transmission to key disease spread parameters for which detailed empirical data is lacking. With parameters at mean values, there is little spread of BTv-8 in Scotland. However, under a “worst case” but still feasible scenario with parameters at the limits of their ranges and temperatures 1 °C warmer than the mean, we find extensive spread with 203,000 sheep infected given virus introduction to the south of Scotland between mid-May and mid-June. Strategically targeted vaccine interventions can greatly reduce BT spread. Specifically, despite BT having most clinical impact in sheep, we show that vaccination can have the greatest impact on reducing BTv infections in sheep when administered to cattle, which has implications for disease control policy

Impact of temperature, feeding preference and vaccination on Schmallenberg virus transmission in Scotland

First identified in 2011, Schmallenberg virus (SBV) is principally transmitted by Culicoides midges and affects ruminants. Clinical presentation is typified by foetal abnormalities, but despite very high infection rates, relatively few animals present with clinical signs. In this paper we further develop a previously published stochastic mathematical model of SBV spread to investigate the optimal deployment of a vaccine for SBV in Scotland, a country that has experienced only sporadic and isolated cases of SBV.We consider the use of the vaccine under different temperatures and explore the effects of a vector preference for feeding on cattle. We demonstrate that vaccine impact is optimised by targeting it at the high risk areas in the south of Scotland, or vaccinating only cattle. At higher than average temperatures, and hence increased transmission potential, the relative impact of vaccination is considerably enhanced. Vaccine impact is also enhanced if vectors feed preferentially on cattle. These findings are of considerable importance when planning control strategies for SBV and also have important implications for management of other arboviruses such as Bluetongue virus. Environmental determinants and feeding preferences should be researched further to inform development of effective control strategies

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

How insects survive the cold: molecular mechanisms - a review

Insects vary considerably in their ability to survive low temperatures. The tractability of these organisms to experimentation has lead to considerable physiology-based work investigating both the variability between species and the actual mechanisms themselves. This has highlighted a range of strategies including freeze tolerance, freeze avoidance, protective dehydration and rapid cold hardening, which are often associated with the production of specific chemicals such as antifreezes and polyol cryoprotectants. But we are still far from identifying the critical elements behind over-wintering success and how some species can regularly survive temperatures below -20°C. Molecular biology is the most recent tool to be added to the insect physiologist’s armoury. With the public availability of the genome sequence of model insects such as Drosophila and the production of custom-made molecular resources, such as EST libraries and microarrays, we are now in a position to start dissecting the molecular mechanisms behind some of these well-characterised physiological responses. This review aims to provide a state of the art snapshot of the molecular work currently being conducted into insect cold tolerance and the very interesting preliminary results from such studies, which provide great promise for the future