Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos

Abstract

Leishmaniases are a group of diseases that affect millions of individuals globally. They are caused by protozoa of the genus Leishmania, mainly transmitted through the bite of vector insects, sandflies. Dogs stand out as the main domestic reservoir of this parasite and can develop the visceral form of the disease. Canine Visceral Leishmaniasis (CVL) can present a wide variety of clinical manifestations, ranging from asymptomatic forms to severe clinical signs. Studies have shown that the clinical progression of CVL is associated with the degree of parasitism in various organs. However, there is still a gap in the scientific literature regarding the threshold of parasitism in dogs that could influence transmission to these vectors. Additionally, it is not known whether there are hematological, immunological, or biochemical biomarkers that may be related to the risk of canine infectivity to sandflies. In Brazil, the Visceral Leishmaniasis Control Program (VLCP) encompasses the diagnosis and treatment of infected humans, vector control, and diagnosis and euthanasia of seropositive dogs. However, the requirement to deliver seropositive dogs to public authorities has been the subject of discussion and protests by owners, who often initiate treatment for CVL, even though it does not eliminate the parasite from their bodies, maintaining the risk of infection to the vector insect. In the current context, the Ministry of Health (MoH) together with the Ministry of Agriculture, Livestock, and Supply (MoAL), authorized the use of a medication for the treatment of dogs with CVL in 2016, Milteforan™. With the expectation of an increase in the number of dogs undergoing CVL treatment in Brazil, it becomes essential to identify biomarkers in CVL that can predict infection by L. infantum to sandflies. The main objective of this research was to evaluate naturally infected dogs with Leishmania infantum, aiming to identify biomarkers associated with resistance or susceptibility, and the possible correlation with the infection of these dogs by sandflies. Additionally, the study included the establishment of a new staging system in CVL, as well as the analysis of various biomarkers in animals with different clinical scores. Forty-seven dogs naturally infected with L. infantum were evaluated, considering hematobiochemical, immunological, clinical, and parasitological aspects. Some biomarkers were identified that showed a positive correlation with the parasitic load observed in sandflies, including: (i) parasitic load in the skin; (ii) in lymph nodes; and (iii) in the spleen; as well as (iv) serum levels of globulin; and (v) alkaline phosphatase. Negative correlation biomarkers were also identified, such as: (i) erythrocyte values; (ii) lymphocytes; (iii) monocytes; and (iv) TCD8+ lymphocyte count. However, the positive correlation was stronger when the animals were categorized according to the severity of clinical signs. This correlation supports the clinical staging system developed in this study as a tool to indicate a high risk of dogs with more severe clinical worsening to infect sandflies with a high parasitic load of L. infantum. This method, being easy to execute and low cost, can be valuable in practical contexts, such as in epidemiological analyses including the development of monitoring and treatment prognosis strategies for canine disease and also contribute to studies related to immunoprotection through vaccines against CVL.