Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

Background
The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP.
Methodology and principal finding
We reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention.
Conclusion and significance
PKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation.

背景
东南亚区域黑热病消除计划（South-East Asia Region Kala-azar Elimination Programme, KAEP）预期将于2017年进入巩固阶段，该阶段核心工作涵盖病例检测、媒介防控以及潜在感染源排查。黑热病后皮肤利什曼病（Post-kala-azar dermal leishmaniasis, PKDL）被认为在内脏利什曼病（visceral leishmaniasis, VL）/黑热病暴发复发中发挥一定作用，而PKDL的防控亦是KAEP的重点任务之一。

研究方法与主要发现
本研究针对亚洲地区PKDL相关文献进行系统回顾，并结合KAEP当前的干预措施对研究结果进行解读，以期提出针对性建议。目前针对VL与PKDL的病理生理学，尤其是其潜在免疫应答机制，仍存在显著的认知空白。其危险因素（其中既往VL治疗或许是最为关键的因素）尚未得到充分阐明，有待进一步明确。PKDL患者在疾病传播中的作用尚不明晰，同时关于皮疹的持续时长、分布范围与严重程度、发病时间以及自愈倾向等关键信息仍存在不足。当前的干预手段以主动病例检测以及采用米替福辛（miltefosine）治疗所有PKDL病例为主，但随着药物耐药性问题日益凸显，该方案面临挑战。目前通过优化VL治疗以预防PKDL的策略尚未得到足够重视。

结论与意义
PKDL是一种异质性且动态变化的疾病，不同患者在内脏利什曼病发病后的发病时间、病程慢性化程度、皮疹分布与外观以及免疫应答（包括自愈倾向）等方面均存在差异，且这些特征可随时间发生变化。为制定最具成本效益的防控策略，需充分阐明其病理生理学机制。应重点早期识别参与疾病传播的患者以及需要接受治疗的患者，并为其提供短疗程、高效且安全的药物治疗方案。需通过创新优化VL治疗手段（包括免疫调节疗法）来强化PKDL的预防工作。