Immunoparasitology series Immunity to Leishmania and the rational search for vaccines against canine leishmaniasis Alexandre B. Reis 1, 2 , Rodolfo C. Giunchetti 1, 2 , Eugenia Carrillo 3 , Olindo A. Martins-Filho 4 and Javier Moreno 3 1 Laborato ´ rio de Imunopatologia, Nu ´ cleo de Pesquisas em Cie ˆ ncias Biolo ´ gicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil 2 Laborato ´ rio de Imunologia Celular e Molecular, Centro de Pesquisas Rene ´ Rachou, FIOCruz, Belo Horizonte, MG, Brazil 3 Unidad de Inmunoparasitologı´a, Centro Nacional de Microbiologı´a, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain 4 Laborato ´ rio de Biomarcadores de Diagno ´ stico e Monitorac ¸a ˜ o, Centro de Pesquisas Rene ´ Rachou, Fundac ¸a ˜ o Oswaldo Cruz, Belo Horizonte, MG, Brazil The control of infection by Leishmania infantum (syn. Leishmania chagasi) in dogs is essential to stop the current spread of zoonotic visceral leishmaniasis. The past few years have seen significant advances in achiev- ing efficient immunization of dogs and, more than ever before, an effective vaccine against canine leishmaniasis can now be considered a feasible goal. This article sum- marizes experimental data gathered from recent dog trials aimed at identifying immunological mechanisms implicated in protection against canine infection to dis- cuss their potential to serve as quantitative surrogate markers of immunization and, more importantly, its usefulness to evaluate whether the immunity induced by the vaccine candidate is strong enough to protect against canine leishmaniasis. Threat to public health by Leishmania-infected dogs Zoonotic visceral leishmaniasis (ZVL), caused by Leish- mania infantum parasites, is a severe infectious disease endemic to Mediterranean countries, the Middle East, Asia and South America. In recent years, ZVL has emerged as an important public health concern owing to the increase in risk factors associated with environmental changes, human migration and the immune status of the host [1,2]. Canines are the main reservoir for the parasite and play a relevant role in transmission to humans. The emergence of human cases of visceral leishmaniasis (VL) in previous non-endemic territories has been preceded by an increase in the incidence of canine infection and the appearance of new foci. Canines have been responsible for the spread of the disease observed in large Brazilian cities where, since the 1980 s, the disease has become endemic and epidemic, resulting in the continuous increase of human cases in Brazil [3]. In Italy, the observed northward spread of leishmaniasis is the consequence not only of climate changes, but also of the increased mobility of dogs to and from ZVL-endemic areas [4]. Moreover, the continued importation of infected dogs has expanded the canine reservoir population to the UK and might allow stable transmission if climate conditions allow the competent vector to survive [5]. The risk of introducing parasite infected dogs in non-endemic areas has become patent in North America, where the possible active transmission of the parasite by indigenous sand flies might have caused the widespread presence of L. infantum-infected foxhounds [6]. Furthermore, given the existence of a stable trans- mission cycle for L. infantum in southern Europe, the introduction and spread in endemic areas of new Leishma- nia species could also be more prevalent. This has recently occurred on the island of Cyprus, where several cases of human leishmaniasis caused by L. donovani MON-37 have been described. This Leishmania parasite was also isolated from infected dogs, which confirms the circulation in a zoonotic cycle of such an ‘imported’ parasite [7]. All these aspects reveal the important threat that both symptomatic and asymptomatic Leishmania-infected dogs represent for public health and that its control is of prime urgency [8]. Control of ZVL is a difficult assignment. Many animals remain asymptomatic after infection, but, in some cases, are still capable of transmitting the parasite, as well as those who develop symptoms of canine leishmaniasis. Current chemotherapy reduces or eliminates clinical symptoms, but does not consistently achieve parasitologi- cal cure in dogs, and the epidemiological risk persists [9]. The culling of seropositive dogs has not prevented the increasing number of human cases in Brazil [3], whereas other measures such as topical insecticides and impreg- nated collars are costly and difficult to implement in a national control programme. Additionally, the available field data do not allow an estimate of their epidemiological impact [10]. In the absence of other successful strategies, the development of vaccines against canine leishmaniasis has been promoted as an important tool and a cost-effective strategy for controlling ZVL [11]. There is increasing awareness that induction in dogs of a protective response Review Corresponding author: Moreno, J. (javier.moreno@isciii.es) 1471-4922/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2010.04.005 Trends in Parasitology 26 (2010) 341–349 341