Contagious ecthyma (CE) is a worldwide highly contagious zoonotic viral skin disease of sheep and goats. Treatment for Orf virus (ORFV) infection usually involves topical and oral antibiotics. An anaesthetic and antiseptic topical gel (Multisolfen® or Tri-Solfen®; MS®, Medical Ethics, Australia) has been documented as an efficacious therapy for lesions from mucosal and epithelial viral infections in ruminants. The present study tested a new treatment protocol of MS® for CE therapy on-farm in 150 lambs naturally infected with ORFV. Lambs were divided into three cohorts of 50 lambs each (C, D and E). Cohort C was treated with MS® 3 times with an interval of 3 days between treatments, cohort D was treated daily with hypochlorous acid, whilst cohort E served as untreated controls. The lambs were examined clinically every two days, weight measured weekly, with whole blood and sterile swabs from ORFV lesions collected for haematological analysis and specific ORFV PCR. Cohort C presented fewer lambs displaying ORFV-associated lesions than other cohorts at different times of the experiment. Further, lesions treated with MS® were milder compared with other cohorts. However, following cessation of therapy, most of the lambs again developed ORFV-associated lesions. No differences between cohorts were observed in weight, haematological and PCR results. These findings suggest that topical treatment with MS® is effective for CE in field conditions, especially in the first stages of the clinical course, although treatment with MS® may need to be extended a minimum of 4 weeks.

Vaccination plays a pivotal role in the control and prevention of animal infectious diseases. However, no efficient and safe universal vaccines are currently registered for major pathogens such as influenza A virus, foot-and-mouth disease virus (FMDV), simian immunodeficiency virus (SIV), and small ruminant lentiviruses (SRLV). Here, we review the development of Sendai virus (SeV) vectors as a promising vaccine platform for animal diseases. Recombinant SeV vectors (rSeVv) possess several key features that make them highly suitable for developing vaccination strategies: (1) SeV has exclusively cytoplasmic replication cycle, therefore incapable of transforming host cells by integrating into the cellular genome, (2) rSeVv can accommodate large foreign gene/s inserts (~5 kb) with strong but adjustable transgene expression, (3) can be propagated to high titers in both embryonated chicken eggs and mammalian cell lines, (4) exhibits potent infectivity across a broad range of mammalian cells from different animals species, (5) undergo transient replication in the upper and lower respiratory tracts of non-natural hosts, (6) has not been associated with disease in pigs, non-humans primates, and small ruminants, ensuring a favorable safety profile, and (7) induce a robust innate and cellular immune responses. Preclinical and clinical studies using rSeVv-based vaccines against influenza A virus, FMDV, SIV, and SRLV have yielded promising results. Therefore, this review highlights the potential of rSeVv-based vaccine platforms as a valuable strategy for combating animal viruses.

Small ruminant lentiviruses (SRLV) cause multisystemic chronic inflammatory disease and significant economic losses in sheep and goats worldwide. However, no vaccines or therapies are currently available. In this study, a recombinant Sendai virus (SeV) vector encoding the SRLV gag-P25 gene (rSeV-GFP-P25) from the EV1 strain was generated using In-FUSION cloning and rescued using the SeV reverse genetic system. Transgene expression and stimulation of innate immunity and interferon-stimulated genes (ovine A3Z1, OBST2 and SAMHD1) were evaluated in ovine skin fibroblasts (OSF) transduced with SeV-GFP and rSeV-GFP-P25. Additionally, to characterize the effect of the SRLV restriction in transduced OSF, the SRLV DNA load was quantified at different times post-transduction and post-infection with strain EV1. Using immunohistochemistry and image analysis, transgene expression and tissue distribution of recombinant P25 were studied in two lambs inoculated intranasally, one with rSeV-GFP-P25 and the other with SeV-GFP. rSeV-GFP-P25 induced efficient and transient transgene expression in vitro and in vivo. Furthermore, OSF transduced with rSeV-GFP-P25 presented upregulation of TLR2, TLR3, TLR6, TLR7, RIG-I, MyD88 and IFN-β, whereas SeV-GFP did not induce TLR6 or IFN-β upregulation. Among the interferon-stimulated genes, OBST2 was significantly upregulated after transduction with rSeV-GFP-P25 compared with the empty vector. SRLV restriction gradually increased and persisted after transduction with SeV-GFP and rSeV-GFP-P25, with OSF transduced three times showing cumulative restriction. Forty-eight hours post-inoculation in vivo, marked P25 expression was observed in ciliated epithelial cells and submucosal macrophages/dendritic cells of the nasal mucosa. This study reinforces the important role of the innate immune response in controlling SRLV infection and suggests that rSeV-GFP-P25 is a potential vaccine candidate against SRLV.

Contagious ecthyma is a highly transmissible eruptive viral disease of the skin and mucosa of sheep and goats distributed worldwide. The treatment of orf lesions is usually based on the use of antiseptics and antibiotics for the management of presumptive secondary infections, increasing risks of antimicrobial resistance. The wound dressing formulation Tri-Solfen^® (TS) containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation has been demonstrated to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease virus infection and reduced the orf viral load in lambs. In the present study, experimental infection with the orf virus was conducted in 50 newborn lambs and 25 animals were treated after the presence of the first lesions with TS and repeated three days later. Daily clinical examination, haematological, serological, biomolecular and post-mortem analyses were conducted during 34 days after treatment. Results indicated that treatment had no effect on weight gain and clinical progression of the lesions. It was determined that seroconversion after experimental infection occurs 34 days after infection and suggested that the deep basal epithelial location of the orf lesions may have prevented the therapy from having altered the clinical course.

Aluminium (Al) hydroxide use as adjuvant induces local formation of long‐lasting subcutaneous granulomas in sheep. Macrophages within these granulomas have been identified as a new small ruminant lentivirus (SRLV) replication site in naturally infected animals. Diagnosis of Al hydroxide‐induced granulomas in sheep is mostly based on postmortem observations but little information is available on in vivo detection. Computed tomography (CT) is used for studying these reactions in other animal species. To determine if CT could be a tool for in vivo diagnosis and research of subcutaneous Al hydroxide‐induced granulomas in sheep. A retrospective survey on thoracic CT scans was performed on 46 adult sheep. Analysis included absence or presence, number and location of subcutaneous nodules. Thoracic CT scans and pathological studies were prescribed to two further sheep. Single or multiple subcutaneous nodules were detected in 26 (56.52%) sheep. One or two nodules per animal were most often observed (36.95%). Size ranged between 1.5 and 4.5 cm. Pre‐contrast two‐dimensional (2D) CT images showed focal or multifocal increases in subcutaneous tissue thickness. Post‐contrast 2D CT images revealed hypointense areas in the centre. Histopathology indicated the presence of granulomas composed by a large number of activated macrophages, surrounding a central core of necrosis. Large intracytoplasmic Al‐positive aggregates were demonstrated by lumogallion staining. CT is a useful tool to detect subcutaneous Al hydroxide‐induced granulomas in vivo in sheep. CT provides a diagnostic and research tool that can be very useful in future works in Al hydroxide‐induced pathology, SRLV infection, or both.

The increasing prevalence of non-healing infected wounds has become a serious concern in the clinical practice, being associated to population aging and to the rising prevalence of several chronic conditions such as diabetes. Herein, the evaluation of the bactericidal and antibiofilm effects of the natural antiseptic terpenes thymol and farnesol standing alone or in combination with the standard care antiseptic chlorhexidine was carried out both in vitro and in vivo. The in vitro combinatorial treatment of chlorhexidine associated with those terpenes against Staphylococcus aureus in its planktonic and sessile forms demonstrated a superior antibacterial activity than that of chlorhexidine alone. Real-time in vivo monitoring of infection progression and antimicrobial treatment outcomes were evaluated using the bioluminescent S. aureus strain Xen36. In vivo studies on infected wound splinting murine models corroborated the superior bactericidal effects of the combinatorial treatments here proposed. Moreover, the encapsulation of thymol in electrospun Eudragit® S100 (i.e., a synthetic anionic copolymer of methacrylic acid and ethyl acrylate)-based wound dressings was also carried out in order to design efficient antimicrobial wound dressings.