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在一个非流行地区,使用包括初始别嘌醇单药治疗的两阶段方案治疗的犬利什曼病的生存时间和预后因素。

Survival time and prognostic factors in canine leishmaniosis in a non-endemic country treated with a two-phase protocol including initial allopurinol monotherapy.

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM, Utrecht, The Netherlands.

出版信息

Parasit Vectors. 2023 May 15;16(1):163. doi: 10.1186/s13071-023-05777-2.

Abstract

BACKGROUND

Leishmania infantum is an intracellular protozoan parasite which is endemic in countries of the Mediterranean Basin. Leishmaniosis is increasingly diagnosed in non-endemic areas due to the relocation of dogs from endemic areas and the travel of dogs to and from these areas. The prognosis of leishmaniosis in these dogs may differ from that of those in endemic areas. The aims of this study were (1) to determine the Kaplan-Meier estimated survival time for dogs with leishmaniosis in the Netherlands (a non-endemic country), (2) to determine if clinicopathological variables at the time of diagnosis predicted the survival of these dogs, and (3) to evaluate the effect of a two-phase therapy protocol of allopurinol monotherapy followed by meglumine antimoniate and/or miltefosine in the case of incomplete remission or relapse.

METHODS

The database of the Department of Clinical Sciences of Companion Animals of the Faculty of Veterinary Medicine, Utrecht University was investigated for leishmaniosis patients. Patient records were reviewed for signalment and clinicopathological data at the time of diagnosis. Only treatment-naive patients were included. Follow-up was performed during the study by phone contact and included treatment received and date and cause of death. Univariate analysis was performed using the Cox proportional hazards regression model.

RESULTS

The estimated median Kaplan-Meier survival time was 6.4 years. In the univariate analysis, increases in monocyte, plasma urea and creatinine concentrations, and urine protein to creatinine ratio were all significantly associated with decreased survival time. The majority of patients only received allopurinol monotherapy.

CONCLUSIONS

Canine leishmaniosis patients in our study population in the Netherlands, which is non-endemic for the disease, had an estimated Kaplan-Meier median survival time of 6.4 years, which is comparable to the outcome of other reported therapy protocols. Increased plasma urea and creatinine concentrations and monocyte concentration were statistically associated with an increased risk of death. We conclude that initial allopurinol monotherapy for 3 months should be effective in more than half of canine leishmaniosis cases, provided there is adequate follow-up, and that meglumine antimoniate or miltefosine therapy should be started as the second phase of the protocol in cases where remission is incomplete or there is a relapse.

摘要

背景

利什曼原虫是一种细胞内原生动物寄生虫,在地中海盆地国家流行。由于来自流行地区的狗的重新安置以及狗往返于这些地区,利什曼病在非流行地区的诊断越来越多。这些狗的利什曼病的预后可能与流行地区的狗不同。本研究的目的是:(1)确定荷兰(非流行地区)利什曼病犬的 Kaplan-Meier 估计生存时间;(2)确定诊断时的临床病理变量是否预测这些狗的生存;(3)评估二阶段治疗方案的效果,即在不完全缓解或复发时使用别嘌醇单药治疗,然后使用葡庚糖胺锑酸盐和/或米替福新。

方法

调查乌得勒支大学兽医学院临床科学系的数据库,以寻找利什曼病患者。对患者记录进行了检查,以确定诊断时的年龄、性别和临床病理数据。仅包括未接受治疗的患者。在研究期间通过电话联系进行随访,包括接受的治疗以及死亡日期和原因。使用 Cox 比例风险回归模型进行单变量分析。

结果

估计的 Kaplan-Meier 中位生存时间为 6.4 年。在单变量分析中,单核细胞、血浆尿素和肌酐浓度以及尿蛋白与肌酐比值的增加均与生存时间缩短显著相关。大多数患者仅接受别嘌醇单药治疗。

结论

在我们的研究人群中,荷兰(非流行地区)的犬利什曼病患者估计 Kaplan-Meier 中位生存时间为 6.4 年,与其他报告的治疗方案结果相当。血浆尿素和肌酐浓度以及单核细胞浓度的增加与死亡风险增加统计学相关。我们的结论是,在有足够随访的情况下,最初的 3 个月别嘌醇单药治疗可能对超过一半的犬利什曼病病例有效,并且应在缓解不完全或复发时开始该方案的第二阶段,即使用葡庚糖胺锑酸盐或米替福新治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/10184344/3ff5358c65f8/13071_2023_5777_Fig1_HTML.jpg

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