Zijlstra Eduard E, Alves Fabiana, Rijal Suman, Arana Byron, Alvar Jorge
Drugs for Neglected Diseases initiative, Geneva, Switzerland.
Rotterdam Centre for Tropical Medicine, Rotterdam, the Netherlands.
PLoS Negl Trop Dis. 2017 Nov 16;11(11):e0005877. doi: 10.1371/journal.pntd.0005877. eCollection 2017 Nov.
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.
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.
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.
东南亚地区黑热病消除计划(KAEP)预计将于2017年进入巩固阶段,该阶段重点在于病例发现、病媒控制以及确定潜在感染源。黑热病后皮肤利什曼病(PKDL)被认为在内脏利什曼病(VL)/黑热病疫情复发中起作用,控制PKDL是KAEP的优先事项之一。
我们回顾了亚洲地区关于PKDL的文献,并结合KAEP当前的干预方法对研究结果进行解读,以便提出建议。关于VL和PKDL的病理生理学,尤其是潜在的免疫反应,存在相当大的知识空白。风险因素(其中既往VL治疗可能最为重要)了解不足,需要更好地加以明确。PKDL患者在传播中的作用在很大程度上尚不清楚,关于皮疹持续时间、分布和严重程度、发病时间以及自愈情况的重要性,信息也不充分。当前的干预方法侧重于主动病例发现,并使用米替福新治疗所有PKDL病例,然而耐药性却日益增加。目前,通过改进VL治疗来预防PKDL未得到充分关注。
PKDL是一种异质性且动态变化的疾病,患者在VL后的发病时间、慢性程度、皮疹分布和外观以及免疫反应(包括自愈倾向)等方面存在差异,所有这些都可能随时间而变化。全面描述病理生理学对于就最具成本效益的方法做出明智决策至关重要。应重点早期发现那些参与传播的人和需要治疗的人,应为他们提供短疗程、有效且安全的药物治疗方案。应通过创新和改进VL治疗来强调预防PKDL,这可能包括免疫调节。