一项评估 Leisguard 作为一种免疫治疗药物治疗健康莱什曼原虫血清阳性犬的疗效和安全性的双盲、随机、对照多中心临床试验。

BACKGROUND: Domperidone (Leisguard) is an immunomodulatory drug used as a preventive measure in healthy dogs. However, no studies have been published in healthy Leishmania infantum-seropositive dogs. The aim of this study was to evaluate the clinical efficacy and safety of domperidone as immunotherapy in Leishmania-seropositive healthy dogs. METHODS: Sixty-seven dogs were treated with domperidone at 0.5 mg/kg and 44 dogs received placebo, once daily for 4 consecutive weeks. Monthly treatments were repeated every 4 months until the end of the 1-year follow-up period. Veterinary examinations were performed on days 0, 30, 120, 150, 240, 270 and 360. Samples of blood and urine were collected on days 0, 120, 240 and 360 for routine laboratory tests and quantitative in-house ELISA for the detection of L. infantum-specific antibodies. Furthermore, Leishmania real-time PCR and IFN-γ ELISA were performed at day 0 and the end of the study. Dogs that developed disease were withdrawn from the study and classified as sick dogs. Adverse drug reactions were reported. RESULTS: Thirty dogs developed disease during the follow-up period: 13/67 (19.4%) in the group treated with domperidone and 17/44 (38.6%) in the placebo-treated group (P = 0.03). Low-seropositive dogs treated with domperidone (4/40, 9.1%) were significantly less likely to develop disease compared to low-seropositive dogs treated with placebo (7/24, 29.2%; P = 0.04), while no differences were found between domperidone (9/23, 39.1%) and placebo (10/20, 50%) in medium- to high-seropositive dogs. At the end of the study, a higher proportion of Leishmania PCR-positive dogs was observed in the placebo-treated group (16/33, 48.5%) compared to the domperidone group (13/51, 25.5%; P = 0.04). Furthermore, low-seropositive dogs treated with domperidone with an increase of IFN-γ concentration presented a higher increase than those treated with placebo at the end of the study. Four dogs treated with domperidone presented self-limiting diarrhea. CONCLUSIONS: Healthy dogs with low L. infantum antibody levels treated with domperidone were less likely to develop disease compared to placebo-treated dogs. Furthermore, domperidone presented a good safety profile.

背景：多潘立酮（Leisguard）是一种免疫调节剂药物，用于健康犬的预防措施。然而，在健康的利什曼原虫血清阳性犬中尚未发表相关研究。本研究旨在评估多潘立酮作为免疫疗法在利什曼原虫血清阳性健康犬中的临床疗效和安全性。

方法：67 只犬接受多潘立酮治疗，剂量为 0.5mg/kg，44 只犬接受安慰剂，每日一次，连续 4 周。每月重复治疗，每 4 个月一次，直至 1 年随访结束。在第 0、30、120、150、240、270 和 360 天进行兽医检查。在第 0、120、240 和 360 天采集血样和尿样进行常规实验室检查和定量内部 ELISA 检测利什曼原虫特异性抗体。此外，在第 0 天和研究结束时进行利什曼实时 PCR 和 IFN-γ ELISA。出现疾病的犬被撤出研究并归类为患病犬。报告药物不良反应。

结果：在随访期间，30 只犬患病：多潘立酮治疗组 13/67（19.4%），安慰剂治疗组 17/44（38.6%）（P=0.03）。与安慰剂治疗的低血清阳性犬（7/24，29.2%）相比，接受多潘立酮治疗的低血清阳性犬（4/40，9.1%）发病的可能性显著降低（P=0.04），而在中至高血清阳性犬中，多潘立酮（9/23，39.1%）和安慰剂（10/20，50%）之间未发现差异。在研究结束时，安慰剂治疗组（16/33，48.5%）中利什曼 PCR 阳性犬的比例高于多潘立酮组（13/51，25.5%）（P=0.04）。此外，与安慰剂治疗组相比，接受多潘立酮治疗且 IFN-γ 浓度升高的低血清阳性犬在研究结束时的升高幅度更高。4 只接受多潘立酮治疗的犬出现自限性腹泻。

结论：与安慰剂治疗组相比，接受多潘立酮治疗的低利什曼原虫抗体水平的健康犬更不易患病。此外，多潘立酮具有良好的安全性。