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

<div><p>Background</p><p>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.</p><p>Methodology and principal finding</p><p>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.</p><p>Conclusion and significance</p><p>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.</p></div

Endemic area for VL in India (Muzaffarpur).

<p>(A) People live in close contact with animals that may attract sand flies. (B) Typical houses with walls made of mud. VL, visceral leishmaniasis.</p

Summary of epidemiological studies published from 2000 to 2017 on prevalence, incidence, and interval between onset of PKDL and VL treatment.^a.

<p>Summary of epidemiological studies published from 2000 to 2017 on prevalence, incidence, and interval between onset of PKDL and VL treatment.<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005877#t001fn001" target="_blank">^a</a>.</p

PKDL from Bangladesh: confluent macular rash involving most of the face (courtesy of Dr. Dinesh Mondal).

<p>PKDL; post-kala-azar dermal leishmaniasis.</p

PKDL from India: discrete papules and infiltration of the chin, resulting in a plaque.

<p>PKDL, post-kala-azar dermal leishmaniasis.</p

PRISMA flowchart of inclusion and exclusion of articles for the review.

<p>PRISMA flowchart of inclusion and exclusion of articles for the review.</p

Survival analysis of time to healing of cutaneous leishmaniasis lesions.

<p>Survival analysis of time to healing of cutaneous leishmaniasis lesions.</p

ALI as a potential reservoir for transmission in the Indian subcontinent.

<p>ALI as a potential reservoir for transmission in the Indian subcontinent.</p

Sandfly abundance, infectiveness, risk factors and effects of vector control strategies.

<p>Sandfly abundance, infectiveness, risk factors and effects of vector control strategies.</p

Relapse following VL and PKDL in the Indian subcontinent.

<p>Relapse following VL and PKDL in the Indian subcontinent.</p