Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Abstract

Introduction:The treatment of leishmaniasis ischallenging, given the diffi culties in drug administration and resistance. Therefore, we chose to test the effi cacy of miltefosine combined with pentoxifylline. Methods: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/ kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. Results: The number of viable Leishmania reduced signifi cantly within the miltefosine-pentoxifylline group (p < 0.05). Conclusions: There is hope that a viable treatment exists for Leishmania infection.

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

“…22 Immunomodulators have been investigated as drugs for the clinical treatment of leishmaniasis, but with limited efficacy when administered alone. 23,24 Guanidines associated with a lethal outcome of the disease, preceding death in patients with visceral leishmaniasis (VL). 26 High levels of IFN-γ, IL-10, and IL-6 are associated with human visceral leishmaniasis and with leishmaniasis persistence.…”

A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis

“…It affects the phospholipid membrane integrity and mitochondrial function of microorganisms ( Sundar et al., 2002 ; Soto et al., 2004 ; Chrusciak-Talhari et al., 2011 ; Sampaio et al., 2019 ). It also has an indirect effect by acting as an immunomodulator against Leishmania, promoting the production of IFN-γ, TNF-α and IL-12 and stimulating phagocytosis and the Th1 pathway ( Santarem et al., 2014 ).…”

“…Pentoxifylline is a methylxanthine with anti-inflammatory effects that suppresses TNF-α gene transcription, increases nitric oxide production and decreases leukocyte migration and adhesion. It is known to have an adjuvant immunologic effect when associated with pentavalent antimony for the treatment of mucocutaneous leishmaniasis ( González et al., 2009 ; Santarem et al., 2014 ; Burza et al., 2018 ). It also has a nephroprotective effect when associated with PAs ( Santarem et al., 2014 ).…”

Análise epidemiológica da Leishmaniose visceral humana no Brasil: contribuição as políticas de controle

“…Contudo, ainda não há um tratamento considerado como adequado para a LV, sendo esta uma questão importante nas falhas observadas no controle da doença, principalmente nas regiões em que o homem é o principal reservatório. [35][36] As estratégias de controle recomendadas pelo Programa Nacional de Controle da LV são direcionadas nos seguintes eixos de atuação: a detecção precoce e tratamento de casos humanos, investigação sorológica de cães domésticos, controle vetorial e também programas de educação em saúde. Considerando que a doença ainda apresenta uma situação epidemiológica preocupante marcada por uma alta letalidade, muitos autores discutem a eficácia dessas medidas, principalmente no tocante à política de eliminação de animais infectados e doentes.…”

“…225 Cerca de 20 a 30 % podem desenvolver manifestações clínicas que variariam desde indivíduos oligossintomáticos até com a sintomatologia mais intensa. 36,226 A LVH apresenta-se clinicamente como doença de evolução arrastada, caracterizada por febre baixa recorrente, tosse seca, sudorese e prostração. Outras manifestações clínicas se desenvolvem com a progressão da doença, em especial a diarréia, ícterícia e edema periférico.…”