Balestrino, Ines (2025) Leishmaniosis in companion animals: new insights with special focus on feline leishmaniosis. [Tesi di dottorato]

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Abstract

Leishmaniosis represents one of the most significant parasitic diseases affecting both human and animal populations worldwide. Caused by protozoa of the genus Leishmania and transmitted through the bite of infected phlebotomine sand flies, it encompasses a broad spectrum of clinical manifestations ranging from self-limiting cutaneous lesions to severe visceral and systemic disease. The complexity of leishmaniosis arises from the intricate interplay among parasite species, vector ecology, host immune responses, and environmental determinants that collectively shape its epidemiology and clinical outcomes. Over the past decades, the global distribution of leishmaniosis has undergone remarkable transformations. Once confined to tropical and subtropical areas, the disease has expanded into temperate regions, particularly across the Mediterranean basin, driven by climatic changes, urbanization, and human and animal mobility. Among the causative agents, Leishmania infantum is recognized as the predominant species responsible for zoonotic visceral leishmaniosis (ZVL) in southern Europe, the Middle East, and Latin America. Within this epidemiological framework, domestic dogs (Canis familiaris) serve as the principal reservoir hosts, sustaining the parasite’s life cycle and representing a major source of infection for sand flies and, consequently, humans. Canine leishmaniosis (CanL) has long been a focal point of veterinary research due to its high prevalence in endemic areas and its relevance as a zoonotic reservoir. Clinically, CanL presents a highly variable course, influenced by host genetics, immune status, parasite virulence, and co-infections. Despite substantial advances in diagnostic techniques—ranging from serological assays to molecular and parasitological tools, standardization remains challenging. Similarly, therapeutic management continues to evolve, with growing interest in immunomodulatory and vaccine-based strategies alongside conventional chemotherapy. The multifaceted nature of CanL underscores the importance of adopting a multidisciplinary approach encompassing epidemiology, immunopathology, clinical management, and public health surveillance. While CanL has been extensively investigated, feline leishmaniosis (FeL) has historically received less attention, being considered sporadic or of limited epidemiological relevance. However, in recent years, an increasing number of studies have documented natural infections in cats, suggesting that felines may play a more active role in the eco-epidemiology of Leishmania spp. than previously believed. Although cats are generally more resistant to infection, they can develop both subclinical and overt disease, sometimes with severe clinical consequences. The immune mechanisms underlying feline susceptibility remain only partially understood, and diagnostic interpretation is often complicated by low or fluctuating antibody titers, atypical clinical signs, and frequent co-infections with retroviruses such as FIV (Feline Immunodeficiency Virus) and FeLV (Feline Leukemia Virus). These aspects highlight the need for further research on the epidemiological significance of feline infection, its clinical expression, and its contribution to the zoonotic cycle of Leishmania spp. Within this context, the present thesis aims to provide a comprehensive and integrative investigation of leishmaniosis in dogs and cats, combining a critical review of existing literature with original research studies that contribute novel insights into epidemiology, diagnosis, and control of the disease in endemic areas. The first part of the thesis provides a general overview of Leishmania spp. parasites, encompassing their taxonomy, morphology, biological cycle, and interactions with vectors and reservoir hosts. It also examines the mechanisms of pathogenesis and the immunological responses elicited during infection, establishing the biological framework for understanding host–parasite dynamics. The second part is dedicated to CanL summarizing current knowledge on its epidemiology, transmission pathways, clinical spectrum, diagnostic approaches, and therapeutic strategies. This section also explores innovative diagnostic tools and biomarkers, as well as supportive therapeutic options such as antioxidant, nutritional, and probiotic supplementation. Importantly, two original studies are presented: • “First detection of Leishmania major in dogs living in an endemic area of zoonotic cutaneous leishmaniosis in Tunisia” — a study that provides the first documented evidence of L. major infection in dogs within a natural transmission setting, challenging the traditional assumption that L. major is strictly anthroponotic and expanding current understanding of its host range and epidemiological relevance. • “Evaluation of the impact of combination of Letifend® vaccine + Scalibor® collar on canine leishmaniosis prevalence in field condition” — an applied field investigation assessing the synergistic effect of combining vaccination and vector control measures in reducing CanL prevalence under natural exposure conditions. This work offers valuable data for refining integrated prevention strategies in endemic regions. The third part focuses on FeL, offering an updated synthesis of current evidence regarding its vectors, epidemiology, immune responses, clinical features, diagnostic challenges, and therapeutic options. It discusses the emerging recognition of cats as potential secondary reservoirs of Leishmania spp., with possible implications for human and canine infection. This section also includes two original contributions: • “Feline leishmaniosis: literature review and survey among veterinarians”, which combines a systematic analysis of existing studies with a professional survey exploring veterinarians’ awareness, diagnostic practices, and perceptions regarding FeL in endemic areas. This research underscores the knowledge gaps and diagnostic uncertainties that persist in clinical practice. • “High seroprevalence of FeL in Campania region: current epidemiological scenario”, a field-based study providing updated seroepidemiological data on FeL in southern Italy. The results reveal a higher-than-expected prevalence of infection, offering new insights into the epidemiological dynamics of Leishmania infantum in domestic cats and reinforcing the need for enhanced surveillance. Collectively, these investigations emphasize the originality and multidisciplinary scope of this thesis, which bridges the gap between canine and feline leishmaniosis, integrates classical and innovative diagnostic approaches, and contributes new field-based evidence to the epidemiological understanding of the disease. Finally, the thesis advocates for a One Health perspective, recognizing that leishmaniosis cannot be effectively addressed without coordinated efforts across veterinary, medical, and environmental disciplines. By deepening our knowledge of leishmaniosis in companion animals and its zoonotic implications, this work aims to support more effective prevention, control, and public health strategies in endemic regions.

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