The involvement of TLR2 and TLR4 in cytokine and nitric oxide production in visceral leishmaniasis patients before and after treatment with anti-leishmanial drugs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nitric oxide and brazilian propolis combined accelerates tissue repair by modulating cell migration, cytokine production and collagen deposition in experimental leishmaniasis

The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy)(2)imN(NO)](PF6)(3)) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.

A comparison of mucosal surface area and villous histology in small intestines of the brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Molecular detection of the blood meal source of sand flies (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis, Parana State, Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Development, characterization, and in vitro biological performance of fluconazole-loaded microemulsions for the topical treatment of cutaneous leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spatial epidemiology of American cutaneous leishmaniasis in a municipality of west Sao Paulo State, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Occurrence of Lutzomyia longipalpis (Phlebotominae) and canine visceral leishmaniasis in a rural area of Ilha Solteira, SP, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative evaluation of several methods for Canine Visceral Leishmaniasis diagnosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serological detection of Toxoplasma gondii, Leishmania infantum and Neospora caninum in cats from an area endemic for leishmaniasis in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Challenges in the therapy of visceral leishmaniasis in Brazil: a public health perspective

Over 3,000 yearly cases of Visceral Leishmaniasis (VL) are reported in Brazil. Brazilian Public Health System provides universal free access to antileishmania therapeutic options: Meglumine Antimoniate, Amphotericin B deoxycholate, and Liposomal Amphotericin B. Even though Amphotericin formulations have been advised for severe disease, this recommendation is mostly based on the opinion of experts and on analogy with studies conducted in other countries. Presently, there are two ongoing multicenter clinical trials comparing the efficacy and safety of the available therapeutic options. Some other issues require further clarification, such as severity markers and the approach to VL/AIDS coinfection. Brazil is facing the challenge of providing access to diagnosis and adequate treatment, in order to avoid VL-related deaths.

Morphological changes in the bone marrow of the dogs with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Novel markers of inflammatory response and hepatic dysfunction in canine leishmaniasis

Dogs are the main host of Leishmania infantum, and the clinical presentation may range from asymptomatic to systemic manifestations. The immune mechanisms in infected, but clinically healthy dogs, prevails Th1 response mediated by cytokines. In this sense, adenosine deaminase (ADA) and butyrylcholinesterase (BChE) are considered as key enzymes in several physiological processes, including the modulation of inflammatory process. Considering the variable immune response against Leishmania and the known participation of ADA and BChE, the aim of this study was to assess the relation between these two enzymes with the inflammatory response as well as hepatic function in dogs naturally infected with L. infantum. For this purpose, the activity of ADA and BChE was assessed in sera of 24 dogs naturally infected with L. infantum, plus 17 healthy dogs. The naturally infected dogs had clinical signs compatible with leishmaniasis and sera activities of ADA (P<0.01) and BChE (P<0.05) decreased, when compared to the healthy group. The reduction of ADA activity probably represented an effect on inflammatory response, especially due to the decreased hydrolysis of extracellular adenosine, might in order to protect against tissue damage and, also, setting a down-regulation on pro-inflammatory cytokines. BChE enzyme had no effect on modulating the immune response in leishmaniasis, but it decreased, a fact may related to deficiency of synthesis in the liver. Therefore, ADA and BChE activities reduced probably in order to protect against extra tissue damage and due failure in synthesis, respectively.

The shadows of a ghost: a survey of canine leishmaniasis in Presidente Prudente and its spatial dispersion in the western region of São Paulo state, an emerging focus of visceral leishmaniasis in Brazil

Visceral leishmaniasis is an emerging zoonosis and its geographic distribution is restricted to tropical and temperate regions. Most of the individuals infected in Latin America are in Brazil. Despite the control measures that have been adopted, the disease is spreading throughout new regions of the country. Domestic dogs are involved in the transmission cycle and are considered to be the main epidemiologic reservoir of Leishmania infantum (syn. L. chagasi). Our aim was to determine the prevalence of canine leishmaniasis (CL) and Ehrlichiosis infection in Presidente Prudente as well as the spatial dispersion of the disease in the western region of São Paulo state. Dogs underwent clinical examination and symptoms related to CL were recorded. Anti- Leishmania antibodies were detected using ELISA, rK39-immunocromatographic tests (DPP), and an indirect fluorescent antibody test (IFAT). Anti-E. canis antibodies were detected by IFAT. A follow-up was conducted in dogs that were positive in the ELISA at the baseline study. Data on the spatial distribution of L. longipalpis and CL in São Paulo state were obtained from Brazilian public health agencies. Serum samples from 4547 dogs were analyzed. The seroprevalence of CL was 11.2 % by ELISA and 4.5 % by IFAT. In the follow-up, seroprevalence was 32.9 % by ELISA, 15.3 % by IFAT, 11.8 % by DPP test, and 66.5 % for E. canis. There was a significant positive association between Leishmania and E. canis infection (P < 0.0001). In the follow-up, clinical examinations revealed symptoms compatible with CL in 33.5 % of the dogs. L. longipalpis was found in 24 and CL in 15 counties of the Presidente Prudente mesoregion. The dispersion route followed the west frontier of São Paulo state toward Paraná state. Low CL and high ehrlichiosis prevalence rates were found in Presidente Prudente city. This emerging focus of CL is moving through the western region of São Paulo state toward the border of Paraná state. Integrated actions to fight the vector, parasites, infected dogs, and humans are needed to monitor the disease and implement strategies for epidemiologic control.

Comparison of diferent diagnostic tests in dogs uninfected and naturally infected with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)