AUTHOR=Mazzotta Elisa , Furlanello Tommaso , Mazzei Alissa , Barberio Antonio , Martignago Federico , Campalto Mery , Foiani Greta , Moronato Maria Luisa , Battistella Claudio , Santinon Elisa , Sabia Michela , Carta Valentina , Boniotti Maria Beatrice , Di Marco Federico , Cabibbe Andrea Maurizio , Cirillo Daniela Maria , Natale Alda TITLE=Case Report: Epidemiologically inferred reverse zoonosis and intra-household zoonotic re-exposure of Mycobacterium tuberculosis in a domestic dog: a one health alert and the diagnostic potential of hypercalcaemia JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 13 - 2026 YEAR=2026 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2026.1824722 DOI=10.3389/fvets.2026.1824722 ISSN=2297-1769 ABSTRACT=BackgroundCanine tuberculosis caused by Mycobacterium tuberculosis is rare and often underdiagnosed. This case report aims to describe the clinical, pathological, and molecular features of a dog with systemic tuberculosis, highlighting its epidemiological relevance within a One Health framework. The specific objective is to characterise a confirmed case of systemic M. tuberculosis infection in a dog, emphasising its unique clinicopathological features, including hypercalcaemia, and documenting an inferred reverse zoonotic transmission with subsequent intra-household zoonotic re-exposure.MethodsA 4-year-old male American Staffordshire terrier presented with lethargy, acute vomiting, anorexia, weight loss, generalised muscle atrophy, ataxia, and a history of chronic cough, orthopaedic disease, and dermatopathy treated with corticosteroids. Clinical evaluation revealed hypercalcaemia, oxaluria, proteinuria, and chronic respiratory and dermatological signs. Cytology showed granulomatous inflammation with intracytoplasmic negatively staining bacilli, raising suspicion for mycobacterial infection. Due to clinical deterioration, euthanasia was performed. Gross and histopathology revealed disseminated granulomatous hepatitis, nephritis, prostatitis, splenitis, and pneumonia with extensive caseous necrosis and mineralization. Ziehl–Neelsen staining confirmed intralesional acid-fast bacilli. Molecular diagnostics (PCR/RFLP, cgMLST) identified Mycobacterium tuberculosis complex (MTBC), and whole-genome sequencing revealed drug-susceptible M. tuberculosis lineage 4.1.2.1 (Haarlem), unrelated to other local strains. Epidemiological investigation supported reverse zoonotic transmission from an infected owner, with possible secondary transmission to a cohabiting individual.ConclusionThis case provides a detailed description of systemic canine tuberculosis and highlights hypercalcaemia as a potentially useful clinicopathological clue in veterinary patients with systemic granulomatous disease due to M. tuberculosis. The evidence supports a reverse zoonotic transmission of M. tuberculosis from human to dog, followed by onward zoonotic transmission to a cohabiting person who developed latent infection. This case underscores the importance of integrated cross-species epidemiological surveillance and the need to strengthen diagnostic and tracing protocols for companion animals within a One Health perspective.