Improving detection and diagnosis of maedi-visna virus infection in sheep in Norway

The main aim of the project is to improve laboratory diagnostics, disease control and surveillance, and thereby contribute to eradicate maedi in Norway. Maedi virus causes chronic pneumonia and weight loss in sheep. The virus came to Norway with imported sheep from Denmark in the 60s and 70s, and the disease was officially reported for the first time in Norway in 1972. Despite active eradication, disease control and surveillance, we have had two major outbreaks of maedi since then- one in Western Norway in the mid-90s, and one in Trøndelag in 2002-2005. In 2003, a national surveillance program for maedi was established. In the surveillance program, blood samples are examined for antibodies against the virus, and in recent years just under 10,000 sheep have been examined annually in the program. In the surveillance program, in June 2019, maedi was again detected in a herd in Trøndelag. An outbreak investigation initiated by the Norwegian Food Safety Authorities, revealed several infected herds in the area. Genetic analyses of the virus from the outbreak of 2019 show that it is closely related to that of the 2002-2005 outbreak. This indicates that the virus has been circulating in the area since then, without being detected in the surveillance program. The nature of maedi, with slowly developing pneumonia and delayed antibody production, makes the diagnostics challenging. An important aim of the project is therefore to improve the ability to detect infected sheep, especially in herds with low prevalence. The project will compare different blood tests for maedi, and evaluate them for use on Norwegian samples. In addition, knowledge of the virus's genetic material will be used to develop a tailor-made test for the 2019 outbreak virus. Furthermore, the project will develop improved tools for outbreak investigation and mapping in order to optimize efficiency of future eradication and surveillance programs.

There is an ongoing maedi outbreak in Norway. The outbreak poses the most serious threat to the Norwegian sheep industry in the last decade. The nature of the infection, with a slow seroconversion, fluctuating antibody response, and individual differences in the immune response of sheep to viral epitopes make diagnosis and control of maedi challenging. Moreover, the virus was last detected in Norway in 2005, but preliminary genetic analyses indicate that the virus has persisted at low levels in the sheep population since that time, evading detection despite continuous surveillance. It is therefore highly relevant to evaluate if we can improve the design of mapping and surveillance programs to optimize the detection of truly infected individual sheep at a manageable cost. The overall aim of the project is improved national preparedness in the context of maedivirus infections. This project will: • Improve the ability to detect infected sheep in herds with low prevalence, by (1) comparing the performance of 3 commercially available ELISA tests in the current Norwegian outbreak by using latent class analysis; and (2) performing the first large-scale mapping of the immune response to different viral epitopes to improve strategies for serological screening. A multiplex assay will be established and made available for diagnostic purposes. • Characterize currently circulating Norwegian maedivirus isolates to identify the need for tailor-made diagnostic solutions and explore phylogenetic relationships • Design more precise computational models to predict the implications of different sampling and test regimes and map in-herd infection dynamics, including identifying risk factors for infection. • Design of outbreak investigation tools and of future control programmes The project will contribute to a more precise serological maedi diagnosis and improved tools for control and surveillance