BACKGROUND The mechanism of resistance to SbIII in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (SbIII)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS The phagocytic capacity and intracellular NO production by classical (CD14++CD16-) and proinflammatory (CD14++CD16+) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(β1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the SbIII-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.

Abstract: INTRODUCTION: Acceptance of the IT LEISH(r) and direct agglutination test- made in the Laboratório de Pesquisas Clínicas (DAT-LPC) by healthcare professionals and patients suspected of visceral leishmaniasis (VL) in Ribeirão das Neves was evaluated. METHODS: Ninety-two patients and 47 professionals completed three questionnaires. RESULTS: Eighty-eight (96%) patients considered fingertip blood collection a positive test feature, and 86% (37) and 91% of professionals considered the IT LEISH(r) easy to perform and interpret, respectively. All professionals classified the DAT-LPC as simple and easy. CONCLUSIONS: Patients and healthcare professionals in Ribeirão das Neves demonstrated a high degree of acceptance of the IT LEISH(r) and DAT-LPC.

Resumo Este trabalho relata o processo e os custos da implantação de dois testes para descentralizar o diagnóstico da leishmaniose visceral (LV) em um município endêmico no Brasil: um teste rápido (IT LEISH) e um teste de aglutinação direta (DAT-LPC). A implantação iniciou com o treinamento dos profissionais de saúde do município na realização dos testes diagnósticos. Os itens incluídos nas estimativas de custo das capacitações foram a remuneração proporcional de todos os profissionais envolvidos e os custos diretos dos testes usados. O estudo foi conduzido entre novembro de 2011 e novembro de 2013. Durante esse período, 17 capacitações foram realizadas e 175 profissionais treinados. O custo relacionado a cada profissional de saúde capacitado na realização do IT LEISH foi de US$ 7,13 e na realização do DAT-LPC, de US$ 9,93. O custo direto do IT LEISH e do DAT-LPC foi estimado em US$ 6,62 e US$ 5,44, respectivamente. Esta primeira avaliação da implantação desses dois testes aponta para a viabilidade da descentralização de ambos os métodos, que aumentam o acesso ao diagnóstico da LV no Brasil.

Abstract This work reports the process and costs of comprehensively implementing two tests to decentralize the diagnosis of visceral leishmaniasis (VL) in an endemic city in Brazil: a rapid test (IT LEISH) and a direct agglutination test (DAT-LPC). The implementation began by training health professionals to perform the tests. Estimation of the training costs considered the proportional remuneration of all professionals involved and the direct costs of the tests used for training. The study was conducted between November 2011 and November 2013. During that time, 17 training sessions were held, and 175 professionals were trained. The training cost for each professional was US$ 7.13 for the IT LEISH and US$ 9.93 for the DAT-LPC. The direct costs of the IT LEISH and DAT-LPC were estimated to be US$ 6.62 and US$ 5.44, respectively. This first evaluation of the implementation of these diagnostic tests indicates the feasibility of decentralizing both methods to extend access to VL diagnosis in Brazil.

Resumen Este trabajo relata la puesta en funcionamiento y los costos de pruebas de diagnóstico de VL en un municipio endémico en Brasil: el test rápido (IT LEISH) y la prueba de aglutinación directa (DAT-LPC). Esta puesta en marcha comenzó por capacitar al personal sanitario del municipio para la realización de las pruebas. Para estimar los costos de la capacitación, se consideró la remuneración proporcional de todo el personal involucrado y los costos directos derivados de la aplicación de las pruebas. El estudio fue realizado entre noviembre de 2011 y noviembre de 2013. En ese periodo se realizaron 17 capacitaciones y se formaron 175 profesionales. Se calcula que el costo derivado de capacitar cada profesional para realizar el IT LEISH fue de 7.13 US$ y 9.93 US$ para el DAT-LPC. Los costos directos del IT LEISH y del DAT-LPC se estimaron en 6,62 US$ y 5,44 US$ respectivamente. La primera evaluación de la puesta en funcionamiento de las dos pruebas en este municipio señala que es viable descentralizar su realización, lo que amplía el acceso al diagnóstico de la VL en Brasil.

Resumo Este trabalho relata o processo e os custos da implantação de dois testes para descentralizar o diagnóstico da leishmaniose visceral (LV) em um município endêmico no Brasil: um teste rápido (IT LEISH) e um teste de aglutinação direta (DAT-LPC). A implantação iniciou com o treinamento dos profissionais de saúde do município na realização dos testes diagnósticos. Os itens incluídos nas estimativas de custo das capacitações foram a remuneração proporcional de todos os profissionais envolvidos e os custos diretos dos testes usados. O estudo foi conduzido entre novembro de 2011 e novembro de 2013. Durante esse período, 17 capacitações foram realizadas e 175 profissionais treinados. O custo relacionado a cada profissional de saúde capacitado na realização do IT LEISH foi de US$ 7,13 e na realização do DAT-LPC, de US$ 9,93. O custo direto do IT LEISH e do DAT-LPC foi estimado em US$ 6,62 e US$ 5,44, respectivamente. Esta primeira avaliação da implantação desses dois testes aponta para a viabilidade da descentralização de ambos os métodos, que aumentam o acesso ao diagnóstico da LV no Brasil.

Abstract This work reports the process and costs of comprehensively implementing two tests to decentralize the diagnosis of visceral leishmaniasis (VL) in an endemic city in Brazil: a rapid test (IT LEISH) and a direct agglutination test (DAT-LPC). The implementation began by training health professionals to perform the tests. Estimation of the training costs considered the proportional remuneration of all professionals involved and the direct costs of the tests used for training. The study was conducted between November 2011 and November 2013. During that time, 17 training sessions were held, and 175 professionals were trained. The training cost for each professional was US$ 7.13 for the IT LEISH and US$ 9.93 for the DAT-LPC. The direct costs of the IT LEISH and DAT-LPC were estimated to be US$ 6.62 and US$ 5.44, respectively. This first evaluation of the implementation of these diagnostic tests indicates the feasibility of decentralizing both methods to extend access to VL diagnosis in Brazil.

Resumen Este trabajo relata la puesta en funcionamiento y los costos de pruebas de diagnóstico de VL en un municipio endémico en Brasil: el test rápido (IT LEISH) y la prueba de aglutinación directa (DAT-LPC). Esta puesta en marcha comenzó por capacitar al personal sanitario del municipio para la realización de las pruebas. Para estimar los costos de la capacitación, se consideró la remuneración proporcional de todo el personal involucrado y los costos directos derivados de la aplicación de las pruebas. El estudio fue realizado entre noviembre de 2011 y noviembre de 2013. En ese periodo se realizaron 17 capacitaciones y se formaron 175 profesionales. Se calcula que el costo derivado de capacitar cada profesional para realizar el IT LEISH fue de 7.13 US$ y 9.93 US$ para el DAT-LPC. Los costos directos del IT LEISH y del DAT-LPC se estimaron en 6,62 US$ y 5,44 US$ respectivamente. La primera evaluación de la puesta en funcionamiento de las dos pruebas en este municipio señala que es viable descentralizar su realización, lo que amplía el acceso al diagnóstico de la VL en Brasil.

The performances of two rapid tests and a standard serological test for the diagnosis of visceral leishmaniasis (VL) were compared using sera from 193 patients with VL and 85 controls. The Kala-Azar Detect®, IT-LEISH® and IFI-LH® assays showed sensitivities of 88.1%, 93.3% and 88.6%, respectively, and specificities of 90.6%, 96.5% and 80%, respectively. The sensitivity values were similar for both rapid tests, but the specificity and positive predictive values of IT-LEISH® were higher than the corresponding values for IFI-LH®. Both rapid tests showed satisfactory performances and can be used in primary health care settings; however, IT-LEISH® permits the use of whole blood, making this assay more suitable for bedside diagnosis.