Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrP^C) into a misfolded pathological isoform (PrP^Sc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrP^C. Yet by an unknown mechanism, PrP^C can fold into different PrP^Sc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrP^Sc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

In late 2018, an epidemic myxomatosis outbreak emerged on the Iberian Peninsula leading to high mortality in Iberian hare populations. A recombinant Myxoma virus (strains MYXV-Tol and ha-MYXV) was rapidly identified, harbouring a 2.8 kbp insertion containing evolved duplicates of M060L, M061L, M064L, and M065L genes from myxoma virus (MYXV) or other Poxviruses. Since 2017, 1616 rabbits and 125 hares were tested by a qPCR directed to M000.5L/R gene, conserved in MYXV and MYXV-Tol/ha-MYXV strains. A subset of the positive samples (20%) from both species was tested for the insert with MYXV being detected in rabbits and the recombinant MYXV in hares. Recently, three wild rabbits were found dead South of mainland Portugal, showing skin oedema and pulmonary lesions that tested positive for the 2.8 kbp insert. Sequencing analysis showed 100% similarity with the insert sequences described in Iberian hares from Spain. Viral particles were observed in the lungs and eyelids of rabbits by electron microscopy, and isolation in RK13 cells attested virus infectivity. Despite that the analysis of complete genomes may predict the recombinant MYXV strains’ ability to infect rabbit, routine analyses showed species segregation for the circulation of MYXV and recombinant MYXV in wild rabbit and in Iberian hares, respectively. This study demonstrates, however, that recombinant MYXV can effectively infect and cause myxomatosis in wild rabbits and domestic rabbits, raising serious concerns for the future of the Iberian wild leporids while emphasises the need for the continuous monitoring of MYXV and recombinant MYXV in both species.

During the necropsies of Iberian hares obtained in 2018/2019, along with signs of the nodular form of myxomatosis, other unexpected external lesions were also observed. Histopathology revealed nuclear inclusion bodies in stromal cells suggesting the additional presence of a nuclear replicating virus.Transmission electron microscopy further demonstrated the presence of herpesvirus particles in the tissues of affected hares.We confirmed the presence of herpesvirus in 13 MYXV-positive hares by PCR and sequencing analysis. Herpesvirus-DNA was also detected in seven healthy hares, suggesting its asymptomatic circulation.Phylogenetic analysis based on DNA polymerase gene, grouped this virus within the gammaherpesviruses, close to herpesviruses from bats and rodents.We propose to name this new virus Leporid gammaherpesvirus 5 (LeHV-5), according to the International Committee on Taxonomy of Viruses standards.The impact of herpesvirus infection on the reproduction and mortality of the Iberian hare is yet unknown but may aggravate the decline of wild populations caused by the recently emerged natural recombinant myxoma virus.

Wasting disease in small ruminants is frequently detected at slaughterhouses. The wasting disorder is manifested by the deterioration of the nutritional and physiological state of the animal indicated by thinness, emaciation, and cachexia. Evidence of emaciation and cachexia, alone, are pathological conditions leading to carcass condemnation during an inspection. Several diseases are associated with a wasting condition, including scrapie, pseudotuberculosis, tuberculosis, paratuberculosis, Maedi Visna, and tumor diseases. On the other hand, parasitic diseases, nutrition disorders, exposure or ingestion of toxins, metabolic conditions, inadequate nutrition due to poor teeth, or poor alimentary diet are conditions contributing to poor body condition. Classical and atypical scrapie is naturally occurring transmissible spongiform encephalopathies in small ruminants. The etiological agent for each one is prions. However, each of these scrapie types is epidemiologically, pathologically, and biochemically different. Though atypical scrapie occurs at low incidence, it is consistently prevalent in the small ruminant population. Hence, it is advisable to include differential diagnosis of this disease, from other possibilities, as a cause of wasting conditions detected during meat inspection at the abattoir. This manuscript is a review of the measures in force at the abattoir for scrapie control, focusing on the differential diagnosis of gross lesions related to wasting conditions detected in small ruminants during meat inspection.

Animal tuberculosis caused by mycobacteria of the Mycobacterium tuberculosis complex (MTBC) represents a significant challenge to both public and animal health. Although eradication programs focus predominantly on cattle, small ruminants, especially goats, may play a relevant role as reservoirs. This study aimed to characterize tuberculosis cases in small ruminants in Portugal diagnosed at the national reference laboratory for Tuberculosis (Instituto Nacional de Investigação Agrária e Veterinária) over the period from April 2012 to July 2023. In this study, samples from 79 animals suspected of TB (64 goats and 15 sheep) were analyzed by integrating histopathology; bacteriology; and, when applicable, PCR results, thereby allowing the distribution by species to be described, MTBC agents to be identified, and diagnostic agreement to be assessed. Of these samples, 29 positive cases (36.7%) were identified, all of them in goats (45.3% of goats tested), whereas no cases were confirmed in sheep. Mycobacterium caprae was the most frequently identified species (89.7%), followed by Mycobacterium bovis (10.3%). Geographic distribution was concentrated in the Alentejo (48.3%) and Norte (44.8%) regions, where 93.1% of cases occurred. Topographical analysis of lesions revealed respiratory tract involvement (lung and/or thoracic lymph nodes) in 82.7% of positive cases, with gross patterns including caseous/caseocalcified lesions (n = 11), necrosis (n = 9), and nodular granulomatous lesions (n = 10). Agreement between histopathology and bacteriology was 81.5%. Parasitic coinfections were observed in 24.1% of positive cases, complicating histopathological interpretation. The results of this study indicate goats, as opposed to sheep, as non-negligible reservoirs of TB, suggesting species-level differences that warrant targeted investigation. The predominance of respiratory lesions and the detection of extensive cavitary forms indicate potential aerogenous transmission with implications for multi-host systems. Diagnostic discordance and parasitic interference reinforce the need for combined testing methodologies. It is therefore advisable to consider the integration of goats into tuberculosis surveillance and control programs, with greater relevance in Alentejo and Norte.