Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part one  Gad Baneth, Alexander F. Koutinas, Laia Solano-Gallego, Patrick Bourdeau, Lluis Ferrer  Trends in Parasitology  Volume 24, Issue 7, Pages 324-330 (July 2008) DOI: 10.1016/j.pt.2008.04.001 Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 1 A schematic presentation of the distribution of leishmaniosis among the canine population in an endemic focus, as seen in a cross-sectional study. The peak of the pyramid (orange) consists of a relatively small subset of dogs showing clinical signs of the disease. Seropostive dogs with no signs of disease represent a second subset (beige). Most of the dogs in the clinical disease and the asymptomatic seropositive subsets would be PCR+. A third subset includes asymptomatic PCR+ but seronegative infected dogs (purple), and a fourth subset includes dogs that are seronegative and do not harbor parasites (blue). A minority of dogs might be seropositive and PCR- (not shown in this model). A study from the Island of Mallorca, Spain [5], showed that 13% of the dogs had clinical disease, 26% were seropositive, 63% were PCR positive and 67% had evidence of infection either by serology or by PCR. Trends in Parasitology 2008 24, 324-330DOI: (10.1016/j.pt.2008.04.001) Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 2 Clinical manifestations of symptomatic canine leishmaniosis: (a) purulent keratoconjunctivitis with periocular dermatitis, (b) facial skin lesions with multifocal exfoliative dermatitis, (c) epistaxis, (d) onychogryposis and (e) skin ulceration on the ear. Trends in Parasitology 2008 24, 324-330DOI: (10.1016/j.pt.2008.04.001) Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 3 A view of the complex interaction between the Th1 and Th2 responses in visceral leishmaniosis focused on current understanding of these responses in CanL. Mixed Th1 and Th2 responses occur in infected dogs, and it is assumed that the balance between these responses tilts in the Th2 direction in dogs that succumb to clinical illness, whereas a stronger protective Th1 activity directs to resistance. The cytokines IFN-γ, IL-2 and TNF-α induce macrophage activation and NO killing of parasites in the Th1 response. By contrast, IL-10, TGF-β and IL-4 are involved in the parasite dissemination associated with increased B-cell (B) and plasma-cell (P) activity and hyperglobulinemia related to the Th2 response. Th1 responses are downregulated by IL-10 produced by T-regulatory (Treg) cells. IL-10 also is produced by cells of the Th1 lineage and is proposed to be beneficial in limiting secondary immunopathology triggered by infection, but it also prevents sterile immunity and allows persistence of low-level infection. Trends in Parasitology 2008 24, 324-330DOI: (10.1016/j.pt.2008.04.001) Copyright © 2008 Elsevier Ltd Terms and Conditions