The effect of BCG vaccination in immune responses against visceral leishmaniasis in a natural (canine) model of infection

Led by Dr Javier Salguero Bodes (Public Heath England), with Dr Isadora dos Santos Lima (FIOCRUZ), Assoc Prof Daniela Farias Larangeira (UFBA), Dr Deborah Fraga (FIOCRUZ), Dr Geraldo Sá Oliveira (FIOCRUZ), Dr Washington dos-Santos (FIOCRUZ), and Prof Luiz Freitas (FIOCRUZ)

Project Aims

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis due to frequent complications and the risk of developing into untreated death. It is a zoonosis with high prevalence and wide distribution by the world. In urban areas, the dog is considered the main reservoir of VL due to its close relationship with humans. Canine disease is also considered valuable for the understanding of human disease, since the clinical presentation in both species show similarities.

Several drugs have been used in the treatment of VL; however, some of them are not recommended by the world health organization for use in veterinary medicine, in order to avoid the parasite's resistance to active principles. Immunotherapy involves the use of biological substances or molecules to modulate immune responses in order to achieve prophylactic and / or therapeutic success. Immunotherapy with or without chemotherapy has been used for the treatment of leishmaniasis. Several studies have described that the use of immunotherapy helps to reduce the clinical signs, the dose of drugs and the time of the treatment.

The BCG vaccine is widely used to prevent tuberculosis and originates from attenuated strains of Mycobacterium bovis. The main mechanism of action of BCG induced protection has been described as mediated by Th-1 cells. The BCG vaccine has been studied as a possible immunotherapeutic for the control of leishmaniasis. Studies with murine models have shown that the use of BCG associated with conventional treatment helps to reduce the parasite burden, the severity of clinical manifestations, and helps increasing the resistance of macrophages to infection, also increasing the capacity of these cells to kill the parasite.

The study aims to evaluate the effects of BCG vaccination administration on the clinical presentation and parasite load of naturally infected dogs from an area endemic for visceral leishmaniasis.

Project Outcomes

Clinical signs associated with canine visceral leishmaniasis were present in all of the dogs during the follow up process. There is a change in the clinical course after treatment, but with no statistically significant difference between the groups. Similarly, clinical pathology outcomes are different between groups but with no statistical significance.

Regarding the histological changes observed in the liver, the most frequent alterations were inflammation in the portal spaces, Kupffer cells hyperplasia and hypertrophy, inflammatory infiltrate of lymphocytic mononuclear cells within the sinusoids and the formation of small aggregates. The inflammation in the portal spaces was composed of predominantly lymphoplasmocytic infiltrate. The granulomas in the sinusoids were composed of macrophagic cells, sometimes parasitized, lymphocytes and, in some cases, plasma cells.

Subsequent analysis of the collected samples include immunohistochemical staining for cell phenotyping, in situ hybridization to assess cytokine production, and determination of the humoral immune profile of anti-Leishmania antibodies.