Rosar Amábilli de Souza, Martins Carolina Leite, Menin Álvaro, Reck Carolina, Grisard Edmundo Carlos, Wagner Glauber, Steindel Mário, Stoco Patricia Hermes, Quaresma Patricia Flavia
Department of Microbiology, Immunology and Parasitology, Laboratory of Protozoology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Department of Biosciences and One Health, Federal University of Santa Catarina, Curitibanos, SC, Brazil.
PLoS One. 2025 Jan 9;20(1):e0313167. doi: 10.1371/journal.pone.0313167. eCollection 2025.
In Brazil, Visceral Leishmaniases is caused by Leishmania infantum, and domestic dogs are the main reservoirs in its urban transmission cycle. As an alternative to euthanizing dogs, miltefosine has been used to treat canine visceral leishmaniasis since 2016. In this study, we have assessed the efficacy of miltefosine for treating canine visceral leishmaniasis in a new endemic area through follow-up of naturally infected dogs was evaluated. The clinical, parasitological, and histopathological characteristics of 21 dogs naturally infected with L. infantum were assessed at three time points: on the day before initiating miltefosine treatment (T0), immediately after treatment completion (T1), and 6 months after treatment completion (T2). Three dogs were treated exclusively with miltefosine, while eighteen received combination therapy with miltefosine with other treatments such as allopurinol, domperidone and immunotherapy. Skin biopsies were obtained from the abdomen to assess inflammatory responses and to quantify parasite loads using qPCR. The parasites were isolated using aspirates acquired from popliteal lymph nodes. Molecular and parasitological analyses confirmed the presence of L. infantum in all dogs, validating the effectiveness of skin and lymph node samples for diagnosis. The clinical conditions of the infected animals were improved and the skin parasite load decreased after treatment, even when distinct combination therapies were performed. The histopathological assessment revealed a miltefosine-induced reduction in the inflammatory response and a decrease in amastigotes number. Furthermore, a positive correlation was established between the reduction in parasite load and the enhancement of clinical scoring, as well as a reduction in the skin inflammatory response. Our findings suggest that miltefosine-based combination therapies reduce skin parasite load and improve clinical outcomes, while the dogs treated with miltefosine alone showed increased parasitic load and worsened clinical staging at T2. Considering this data belonging to a recent transmission area, treatment strategy suggests effective in controlling canine visceral leishmaniasis.
在巴西，内脏利什曼病由婴儿利什曼原虫引起，家犬是其城市传播周期中的主要宿主。自2016年以来，作为安乐死犬类的替代方法，米替福新已被用于治疗犬内脏利什曼病。在本研究中，我们通过对自然感染犬的随访，评估了米替福新在一个新的流行地区治疗犬内脏利什曼病的疗效。在三个时间点评估了21只自然感染婴儿利什曼原虫的犬的临床、寄生虫学和组织病理学特征：在开始米替福新治疗前一天（T0）、治疗完成后立即（T1）以及治疗完成后6个月（T2）。三只犬仅接受米替福新治疗，而十八只接受米替福新与其他治疗（如别嘌醇、多潘立酮和免疫疗法）的联合治疗。从腹部获取皮肤活检样本以评估炎症反应，并使用qPCR定量寄生虫载量。使用从腘窝淋巴结获取的抽吸物分离寄生虫。分子和寄生虫学分析证实所有犬均存在婴儿利什曼原虫，验证了皮肤和淋巴结样本用于诊断的有效性。即使进行了不同的联合治疗，治疗后感染动物的临床状况得到改善，皮肤寄生虫载量降低。组织病理学评估显示米替福新可导致炎症反应减轻和无鞭毛体数量减少。此外，寄生虫载量的降低与临床评分的提高以及皮肤炎症反应的减轻之间建立了正相关。我们的研究结果表明，基于米替福新的联合治疗可降低皮肤寄生虫载量并改善临床结局，而仅用米替福新治疗的犬在T2时寄生虫载量增加且临床分期恶化。考虑到这些数据来自一个近期的传播地区，治疗策略表明对控制犬内脏利什曼病有效。
